Significance of the anti-aging protein Klotho.

The Klotho gene was identified as an 'aging suppressor' in mice. Overexpression of the Klotho gene extends lifespan and defective Klotho results in rapid aging and early death. Both the membrane and secreted forms of Klotho have biological activity that include regulatory effects on general metabolism and a more specific effect on mineral metabolism that correlates with its effect on aging. Klotho serves as a co-receptor for fibroblast growth factor (FGF), but it also functions as a humoral factor that regulates cell survival and proliferation, vitamin D metabolism, and calcium and phosphate homeostasis and may serve as a potential tumor suppressor. Moreover, Klotho protects against several pathogenic processes in a FGF23-independent manner. These processes include cancer metastasis, vascular calcification, and renal fibrosis. This review covers the recent advances in Klotho research and discusses novel Klotho-dependent mechanisms that are clinically relevant in aging and age-related diseases.

Vasorelaxant Effects of the Vitex Agnus-Castus Extract.

This study was undertaken to describe and characterize the relaxing effects of the medicinal plant Vitex agnus-castus (VAC) extract on isolated rabbit arterial rings. The VAC extracts (VACE) were extracted with ethanol and tested in aorta rings (3-4 mm) of rabbits suspended in an organ bath (Krebs, 37°C, 95% O2/5% CO2) under a resting tension of 1 g to record isometric contractions. After the stabilization period (1-2 hours), contractions were induced by the addition of phenylephrine (0.5 µM) or high KCl (80 mM) and VACE was added on the plateau of the contractions. Experiments were performed to determine the effects and to get insights into the potential mechanism involved in VACE-induced relaxations. The cumulative addition of VACE (0.15-0.75 mg/mL) relaxed, in a concentration-dependent manner, the rabbit aorta rings precontracted either with phenylephrine- or with high KCl thus suggesting calcium channel blocking activities. The VACE effect appeared to be endothelium-dependent. The preincubation with L-NAME (the inhibitor of nitric oxide synthases (NOS)), ODQ (the selective inhibitor of guanylyl cyclase), and indomethacin (the cyclooxygenase inhibitor), downregulated VACE-induced relaxation of aorta rings precontracted with phenylephrine, whereas the bradykinin (stimulator of NOS) and zaprinast (phosphodiesterase inhibitor) further upregulated relaxant effects induced by VACE. These results revealed that the aorta relaxation effect of VACE was mainly endothelium-dependent and mediated by NO/cGMP and prostaglandins synthesis. This vasodilator effect of VACE may be useful to treat cardiovascular disorders, including hypertensive diseases.

Diastereoselective radical mediated alkylation of a chiral glycolic acid derivative.

Radical alkylation of 2-(tert-butyl)-2-methyldioxolan-4-one, a chiral equivalent of glycolic acid, occurs with good to high diastereoselectivity that compares favorably with the corresponding enolate alkylation. The importance of the position of the transition state position, early or late, is highlighted.

Insight into the Mechanisms Underlying the Tracheorelaxant Properties of the Sideritis raeseri Extract.

Sideritis raeseri Boiss. and Heldr. (Lamiaceae), known as "mountain tea," is a native plant from the Mediterranean region, which is widely used in traditional medicine. This study evaluates the effects of the ethanol extract of Sideritis raeseri (SR) on airway smooth muscle activity and identifies the underlying mechanism. The S. raeseri extract (SRE) was extracted from air-dried parts of the shoot system of SR. The SRE (0.3-2 mg/mL) was tested in isolated rabbit tracheal rings, suspended in the organ bath, filled with Krebs solution, and bubbled with the carbogen mixture (95% O2/5% CO2) under a resting tension of 1 g in 37°C. In in vitro experiments, the SRE relaxed against acetylcholine-induced constriction in tracheal rings. Furthermore, SRE inhibited Ca2+-induced contractions in carbachol (CCh, 1 µM) as well as in the K+-depolarized trachea (80 mM). Our findings showed the NO/cGMP involvement in tracheorelaxant effects of SR. To this end, the effect of the SRE was potentiated by bradykinin (nitric oxide (NO) synthase activator, 100 nM), whereas it was inhibited by ODQ (inhibitor of NO-sensitive guanylyl cyclase, 10 µM) and L-NAME (NO synthase inhibitor, 100 µM), as well as indomethacin (cyclooxygenase inhibitor, 10 µM). These data suggest that the tracheorelaxant effect of the SRE is mediated at least partly by NO/cyclic guanosine monophosphate and cyclooxygenase-1-prostaglandin E2-dependent signaling. These findings indicate that the SRE may be used in various respiratory disorders.

Lignans and indole alkaloids from the seeds of Centaurea vlachorum Hartvig (Asteraceae), growing wild in Albania and their biological activity.

The present phytochemical investigation of the seeds of Centaurea vlachorum led to the isolation and characterisation of four compounds including two indole alkaloids N-(p-coumaroyl) serotonin (1) and moschamine (2) and two dibenzylbutyrolactone lignans matairesinol (3) and arctiin (4). This is the first report on the isolation of non-volatile secondary metabolites from C. vlachorum. The chemataxonomic significance of these compounds was summarised. Moreover, the isolated compounds were tested for their free radical scavenging activity using the following in vitro assays: (i) interaction with the free stable radical of DPPH (1,1-diphenyl-2-picrylhydrazyl), (ii) inhibition of linoleic acid peroxidation with the dihydrochloric acid of 2,2-Azobis-2-amidinopropane (AAPH). Finally, their inhibitory activity towards soybean lipoxygenase was evaluated, using linoleic acid as substrate.

Antioxidant Activity and Chemical Composition of Essential Oils of some Aromatic and Medicinal Plants from Albania.

The chemical compositions have been investigated of the volatile oils of nine populations of six species from Albania, namely Artemisia absinthium, Calamintha nepeta, Hypericum perforatum, Sideritis raeseri subsp. raeseri, Origanum vulgare subsp. hirtum from two wild .populations, and Salvia officinalis (sage) from two wild and one cultivated population,. The essential oils were obtained by hydrodistillation and their analyses were performed by GC-MS. The major constituents were: A. absinthium: neryl isovalerate (19.5%), geranyl isobutanoate (16.4%) and carvacrol (8.8%); C. nepeta: pulegone (31.7%), spathulenol (20.0%) and isomenthone (12.7%); H. perforatum: caryophyllene oxide (31.0%), δ-selinene (10.5%) and carvacrol (10.4%); O. vulgare: carvacrol (81.0, 78.6%), y-terpinene (5.5, 7.1%) and p-cymene (4.9, 4.1%) for 0. vulgare originating from Tepelena. and.Vlora, respectively; S. raeseri: carvacrol (36.7%), caryophyllene oxide (17.8%), p-caryphyllene (8.7%), spathulenol (7.7%) and myrtenol (6.4%); S. officinalis: camphor (40.2, 47.8, 45.9%), c-thujone .(19.2, 22.2, 13.7%), eucalyptol (5.4, 2.6, 6.0%), camphene (5.8, 6.1, 3.9, %), borneol (2.1, 2.9, 5.7%) and bornyl acetate (3.3, 1.4, 5.6%) for samples originating from Tepelena, Tirana and Vlora, respectively. The essential oils were also tested for their free radical scavenging activity using the following in vitro assays: i) interaction with the free stable radical of DPPH (1,1-diphenyl-2-picrylhydrazyl), and ii) inhibition of linoleic acid-peroxidation with 2,2'-azobis- 2-methyl-propanimidamide, dihydrochloride (AAPH). Finally, their inhibitory activity toward soybean lipoxygenase was evaluated, using linoleic acid as substrate.The essential oil of 0. vulgare (OV-VL) presented the highest interaction with the stable radical DPPH (76.5%), followed by that of A. absinthium (54.7%). O. vulgare (OV-TP) and A. absinthium showed high anti-lipid peroxidation activity, 97.5% and 96.5%, respectively, higher than that of the reference compound trolox (73.0%). Only the tested sample of O. vulgare (OV-VL) significantly inhibited soybean lipoxygenase (54.2%).

AMPK-sensitive cellular transport.

The energy sensing AMP-activated protein kinase (AMPK) regulates cellular and whole-body energy balance through stimulating catabolic ATP-generating and suppressing anabolic ATP-consuming pathways thereby helping cells survive during energy depletion. The kinase has previously been reported to be either directly or indirectly involved in the regulation of several carriers, channels and pumps of high significance in cellular physiology. Thus AMPK provides a necessary link between cellular energy metabolism and cellular transport activity. Better understanding of the AMPK role in cellular transport offers a potential for improved therapies in various human diseases and disorders. In this review, we discuss recent advances in understanding the role and function of AMPK in transport regulation under physiological and pathological states.