Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer's disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aβ(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aβ(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aβ(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aβ(1-42) peptide in human erythrocytes and molecular models

Prenyllipids and pigments content in selected Antarctic lichens and mosses

The content and relative composition of tocopherols, plastochromanol, plastoquinone and pigments in fifteen Antarctic species (five mosses and ten lichens) were analyzed by HPLC. Total tocopherols in mosses ranged from 90 mg/g (Warnstrofia sarmentosa) to 220 mg/g (Syntrichia magellanica), while in lichens it ranged from 0.89 mg/g in Caloplaca sp. to 45 mg/g in Placopsis contortuplicata. With the exception of Ochrolechia frigida, in all other mosses and lichens species, a-tocopherol accounted for more than 90 % of total tocopherols. Plastochromanol was detected in four mosses and two lichen species; the highest level was found in Polytrichastrum alpinum (19.1 mg/g). The highest content of plastoquinone-9 (PQ-9) in mosses was found in Bryum pseudotriquetrum (42.6 mg/g), whereas in lichens it was 24.5 mg/g in Stereocaulon alpinum, and 23.17 mg/g in Umbilicaria antarctica. Pigment composition in mosses was typical for higher plants. Some lichen species lacked chlorophyll b, violaxanthin and b-carotene. Based on these results it is suggested that tocochromanols and carotenoid pigments are involved in the protection of mosses and lichens against the oxidative stress caused by the extreme Antarctic conditions

An in vitro study of the antioxidant and antihemolytic properties of buddleja globosa (Matico)

The antioxidant and antihemolytic properties contained in the leaves of Buddleja globosa (B. globosa), also known as "Matico," were determined. Aqueous extracts of leaves were assayed in human erythrocytes and molecular models of its membrane. The latter were bilayers built-up of lipids located in the outer and inner leaflets of the erythrocyte membrane. Observations by scanning electron microscopy showed that the extract altered the morphology of erythrocytes inducing the formation of crenated echinocytes. This result implied that the extract components were inserted into the outer leaflet of the cell membrane. This conclusion was confirmed by experiments carried out by fluorescence spectroscopy of red cell membranes and vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC) and by X-ray diffraction of DMPC and dimyristoylphosphatidylethanolamine bilayers. Human erythrocytes were in vitro exposed to HClO, which is a natural powerful oxidant. Results demonstrated that low concentrations of B. globosa aqueous extract neutralized the harmful capacity of HClO. Hemolysis experiments also showed that the extract in very low concentrations reduced hemolysis induced by HClO.FONDECYT Grant, 109004