No abstract

Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. Here we show that, after injury to the mouse brain, 2-AG may have a neuroprotective role in which the cannabinoid system is involved. After closed head injury (CHI) in mice, the level of endogenous 2-AG was significantly elevated. We administered synthetic 2-AG to mice after CHI and found significant reduction of brain oedema, better clinical recovery, reduced infarct volume and reduced hippocampal cell death compared with controls. When 2-AG was administered together with additional inactive 2-acyl-glycerols that are normally present in the brain, functional recovery was significantly enhanced. The beneficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an antagonist of the CB1 cannabinoid receptor.

No abstract

The autofluorescent lipofuscin that accumulates in retinal pigment epithelial cells with age may contribute to an age-related decline in cell function. The major lipofuscin fluorophore, A2E, is a pyridinium bisretinoid. We previously proposed that the biogenesis of A2E involves the following: (i) formation of the Schiff base, N-retinylidene phosphatidylethanolamine from alltrans-retinal and phosphatidylethanolamine in the photoreceptor outer segment membrane; (ii) further reaction of N-retinylidene phosphatidylethanolamine with retinal to yield phosphatidylethanolamine-bisretinoid, A2-PE; (iii) hydrolysis of A2-PE to generate A2E. To provide evidence for this biogenic scheme, all-trans-retinal was reacted with dipalmitoyl-L-␣-phosphatidylethanolamine to yield DP-A2-PE (A2-PE), as confirmed by UV, with mass spectrometry revealing the molecular ion at m/z 1222.9 (C 77 H 124 O 8 PN) accompanied by product ion at m/z 672.8, representing the phosphoryl-A2E fragment of A2-PE. In reaction mixtures of retinal and outer segments and in samples of Royal College of Surgeons rat retina containing outer segment membranous debris, A2-PE was detected as a series of high performance liquid chromatography peaks, each with UV similar to reference A2-PE. By mass spectrometry, A2-PE consisted of multiple peaks, representing fatty acids with different chain lengths, and the phosphoryl-A2E moiety, m/z 673. Incubation of the retinal/outer segment reaction mixture with phospholipase D generated A2E, as detected by high performance liquid chromatography, thus confirming A2-PE as the A2E precursor.The lipofuscin that accumulates in retinal pigmented epithelial (RPE) 1 cells with age and in some retinal disorders is a complex mixture of fluorophores, some elements of which are derived from molecular components of the photoreceptor cell membrane. These membrane elements become deposited in the RPE cell as a result of the latter's role in phagocytosing packets of outer segment membrane that are shed by the photoreceptor cell during the daily process of membrane renewal. It is now known that a major hydrophobic constituent of RPE lipofuscin is the fluorophore, A2E (1), a pyridinium bisretinoid (2, 3). A2E has been quantified in human donor eyes, and a photoisomer of A2E, iso-A2E, has been characterized (4). For many years, the impact of lipofuscin accumulation on the RPE cell has been poorly understood. Recently, however, we have demonstrated that when A2E is accumulated to critical concentrations by cultured RPE, it can manifest detergent-like activity (5) and can serve as an initiator of blue light-induced cellular damage (6). A2E is generated from all-trans-retinal and ethanolamine, the former being released from photoactivated rhodopsin, and the latter being the head group of phosphatidylethanolamine (PE), an abundant membrane phospholipid (1-3). Nevertheless, the mechanism of production of A2E has not been demonstrated. Similarly, the site of its formation, whether within phagolysosomal compartments of the RPE cell (7,8) or within the p...

Viral infections affect three to five million patients annually. While commonly used antivirals often show limited efficacy and serious adverse effects, herbal extracts have been in use for medicinal purposes since ancient times and are known for their antiviral properties and more tolerable side effects. Thus, naturally based pharmacotherapy may be a proper alternative for treating viral diseases. With that in mind, various pharmaceutical formulations and delivery systems including micelles, nanoparticles, nanosuspensions, solid dispersions, microspheres and crystals, self-nanoemulsifying and self-microemulsifying drug delivery systems (SNEDDS and SMEDDS) have been developed and used for antiviral delivery of natural products. These diverse technologies offer effective and reliable delivery of medicinal phytochemicals. Given the challenges and possibilities of antiviral treatment, this review provides the verified data on the medicinal plants and related herbal substances with antiviral activity, as well as applied strategies for the delivery of these plant extracts and biologically active phytochemicals.

Neun Epoxidringe entstehen nacheinander, wenn A2E mit blauem Licht in Gegenwart von Sauerstoff bestrahlt wird [Gl. (1)]. Mechanistisch gesehen erzeugt A2E Singulettsauerstoff und reagiert mit diesem zu den Polyoxiranen. Das Verständnis der Reaktion von A2E mit Sauerstoff ist wichtig, weil blaues Licht die Apoptose von A2E‐beladenen Zellen des retinalen Pigmentepithels auslöst, die typisch für die altersabhängige Makuladegeneration ist.

We have examined questions related to the biosynthesis of A2E, a fluorophore that accumulates in retinal pigment epithelial cells with aging and in some retinal disorders. The use of in vitro preparations revealed that detectable levels of A2-PE, the A2E precursor, are formed within photoreceptor outer segments following light-induced release of endogenous all-trans-retinal. Moreover, experiments in vivo demonstrated that the formation of A2-PE in photoreceptor outer segment membrane was augmented by exposing rats to bright light. Whereas the generation of A2E from A2-PE by acid hydrolysis was found to occur very slowly, the detection in outer segments of a phosphodiesterase activity that can convert A2-PE to A2E may indicate that some portion of the A2-PE that forms in the outer segment membrane may undergo hydrolytic cleavage before internalization by the retinal pigment epithelial cell. The identities of additional minor components of retinal pigment epithelium lipofuscin, A2E isomers with cis olefins at positions other than the C13-C14 double bond, are also described.The fluorophore A2E, a pyridinium bisretinoid (1, 2), accumulates in retinal pigment epithelial (RPE) 1 cells as a major component (3, 4) of the lipofuscin that is characteristic of senescence and some inherited retinal disorders. Recent evidence indicates that A2E has the potential for causing RPE cell death (5-9) and, as such, may contribute to the RPE cell atrophy that is observed in age-related macular degeneration (10) and retinal degenerative diseases such as Stargardt's disease (11, 12), Best's macular dystrophy (13), and cone-rod dystrophy (14).The biosynthesis of A2E (4, 15) begins in the photoreceptor outer segment (ROS) membrane as a reaction between phosphatidylethanolamine and a single molecule of all-trans-retinal that generates a phosphatidylethanolamine-all-trans-retinal Schiff base conjugate (N-retinylidene-phosphatidylethanolamine). This adduct undergoes a [1,6]-proton tautomerization generating a phosphatidylethanolamine-retinyl enamine, which reacts with a second molecule of all-trans-retinal. After aza-6-electrocyclization and auto-oxidation, the fluorescent phosphatidyl-pyridinium bisretinoid A2-PE is formed. A2-PE was established as the precursor of A2E by HPLC detection of A2E after enzyme-mediated hydrolysis of A2-PE, whereas the structure of A2-PE was confirmed by collision-induced dissociation mass spectrometric analysis (FAB collision-induced dissociation mass spectrometry/MS). The A2-PE that forms in the outer segments leads to the deposition of A2E in RPE cells because of the latter cell's role in phagocytosing the outer segment membrane that is discarded daily by the photoreceptor cell. The tendency for A2E to undergo photoisomerization was illustrated by the identification of iso-A2E, a Z-isomer, at the C13-C14 double bond of one of the hydrophobic retinal chains. In the HPLC profile of human RPE extracted in the dark, iso-A2E is a pigment that is slightly less polar than A2E. Using synthetic samples, iso-A2E has ...

Nowadays, owing to drastic changes in social conditions, people are increasingly becoming stressed. Consequently, the number of people who want to be healed is also increasing. In this study, we focused on the use of plants to reduce stress. We develop a pseudo-communication system with plants using 7 sensors (for temperature, humidity, CO 2 , and so on), a microphone, and a display. The system will have healing effects such as those of counselors or animal-assisted therapy. Then, a communication experiment is carried out to confi rm that the proposed system can reduce user's stress. As a result, from amylase activity, it is found that user stress is reduced when the user uses the system when stressed. Therefore, it is clear that the proposed communication system has some healing effect on stressed users.