Noni as an anxiolytic and sedative: A mechanism involving its gamma-aminobutyric acidergic effects

Noni (Morinda citrifolia) is increasing in worldwide popularity as a food or dietary supplement with versatile health benefits. The aim of this study was to investigate the effects of Noni fruit on anxiety symptoms in vitro. To this end, a competitive GABAa receptor-binding assay was developed. Our preliminary study indicates that the methanol crude extract of Noni fruit showed significant affinity to the gamma-aminobutyric acid A (GABAa) inhibitory neurotransmitter receptors, and displayed 75% binding inhibition of the agonist radioligand [3H] muscimol at a concentration of 100 microg/ml. Further experiments demonstrated that the MeOH extract, and its BuOH and H2O partitions, exhibited IC50 values of 22.8, 27.2, and 17.1 microg/ml, respectively, in the GABAa-binding assay. Experimental results with Noni fruit indicate the presence of competitive ligand(s), which may bind to the GABAa receptor as an agonist, and thus induce its anxiolytic and sedative effects. The study provides an in vitro rationale for one of Noni's versatile and traditional uses. In addition, an HPLC fingerprint profile of the methanolic extract of Noni fruit has been established for quality control purpose.     

Cytokine cross-talk between phagocytic cells and lymphocytes: Relevance for differentiation/activation of phagocytic cells and regulation of adaptive immunity

Cytokines represent one of the most important elements in the communication among different cell types. They play an increasingly better understood role in the communication among hematopoietic cells and in particular in the reciprocal regulation of effector cell types of innate or natural resistance (phagocytic cells and Natural Killer (NK) cells) and those of adaptive immunity (T and B lymphocytes). Lymphocytes produce several cytokines with either stimulatory (e.g., colony stimulatory factor) or suppressive (e.g., tumor necrosis factors and interferons) effects on proliferation of early hematopoietic cells. Many of these cytokines, alone or acting in synergistic combinations, also have a differentiation-inducing ability on immature myeloid cells and act as powerful potentiators of the cellular functions of terminally differentiated phagocytic cells. The communication between lymphocytes and phagocytic cells is not unidirectional, as phagocytic cells produce factors that regulate lymphocyte activation. In addition to their role as antigen presenting cells expressing costimulatory accessory molecules and secreting cytokines (e.g., IL-1, IL-6, TNF), phagocytic cells have been recently shown to produce Natural Killer cell Stimulatory Factor (NKSF/IL-12). IL-12 is a heterodimeric cytokine with important modulatory functions on cytotoxicity of NK and T cells, lymphocyte proliferation, lymphokine production, and development of T helper cell subsets. These communications between phagocytic cells and lymphocytes are further regulated by negative and positive feedback mechanisms that contribute to maintain the homeostasis of the system in physiologic conditions and to govern the changes in this equilibrium needed for the response to infectious or other foreign agents.     

Arabidopsis: Sensitivity of growth to high temperature

Arabidopsis thaliana seedlings as measured by an electrolyte leakage assay, have been found to be extremely sensitive to high temperature stress as compared to a high temperature tolerant variety (Tracy) of soybean. Over 50% ion leakage occurred in Arabidopsis leaves during a 15-minute exposure to 50°C, indicating a heat killing time of less than 15 minutes. In contrast, the heat killing time for soybean at 50°C was over five times longer. When soybean or Arabidopsis seedlings in culture plates were exposed to 37°C for 2 hours and then returned to 23°C, they suffered no apparent short-term or long-term damage. Soybean seedlings given a 42°C, treatment for 2 hours also showed no damage. Arabidopsis seedlings after a 42°C treatment for 2 hours showed no apparent immediate damage, but 48 hours after return to 23°C severe damage symptoms were visible and after 96 hours all the seedlings were dead. Both soybean and Arabidopsis seedlings synthesize heat shock proteins (hsps) when exposed to 42°C for 2 hours. The hsps synthesized are of similar molecular weights, although the relative abundances of the different size classes are very different in the two plants. Even though hsps are produced in Arabidopsis seedlings after a 2 hour exposure to 42°C their presence is not sufficient for the seedlings to recover from the effects of rhe heat shock when returned to 23°C. Our results show that Arabidopsis has a heat sensitive genotype. This along with its other characteristics should make it a good model system in which to assay in transgenic plants, the functions of homologous and heterologous genes that might be candidates for determining heat tolerance in plants.     

Ferredoxin—ferredoxin NADP reductase interaction: Catalytic differences between the soluble and thylakoid-bound complex

Ferredoxin-NADP reductase (FNR) and ferredoxin form a complex when the former is membrane-bound as they do when both components are in solution, with the same dissociation constant. The rate constant of NADP photoreduction, first order with respect to the complex, is more than 20-times higher when FNR is membrane-bound than when the enzyme is in solution. The Arrhenius activation energy is identical in both conditions. These observations are interpreted in terms of ‘entropic catalysis’ of NADP reduction by the thylakoid-bound FNR.     

Arrangement of smooth muscle cells and intramuscular septa in the taenia coli

Summary Bands of electron-dense material beneath the cell membrane of smooth muscle cells of the guinea-pig taenia coli provide attachment to thin myofilaments and to intermediate (10 nm) filaments; about 50% of the cell membrane is occupied by dense bands in muscle cells transversely sectioned at the level of their nucleus, and between 50 and 100% in smaller cell profiles nearer the cell's ends. In addition to the known cell-to-cell junctions (intermediate contacts), more complex apparatuses anchor muscle cells together, either end-to-end or end-to-side or side-to-side. They consist of elaborate folds, invaginations and protrusions accompanied by large amounts of basal lamina material. In the end-to-end anchoring apparatuses numerous finger-like and laminar processes from the two cells interdigitate. Other muscle cells have a star-shaped profile in the last few microns of their length, or show longitudinal invaginations occupied by a thickened basal lamina and occasionally by collagen fibrils. The septa of connective tissue extend only for a few hundred microns along the length of the taenia. In taeniae fixed in condition of mild stretch the muscle cells form an angle of about 5° with the septa. In muscles fixed during isotonic contraction the angle increases to about 20–22°, and in longitudinal sections the muscle cells appear arranged in a herring-bone pattern. The collagen concentration in the taenia coli is 4–6 times greater that in skeletal and cardiac muscles. These various structures are discussed in terms of their possible role in the mechanism of force transmission.I thank Mr. S.J. Sarsfield and Miss E.M. Franke for expert technical assistance, and Dr. Adam Yamey for much help in the experiments on collagen content. This work is supported by grants from the Medical Research Council     

Enkephalin-binding systems in human plasma

Three amino acid-containing fractions present in human plasma are shown to bind both leu and met-enkephalin: serum albumin and two species of a much lower molecular weight, in all likelihood polypeptides. The amount of enkephalin associated with serum albumin seems comparatively smaller than that associated with the two low molecular weight systems. These systems jointly are apparently capable of binding a significant part of the circulating enkephalins. The possibility is suggested that the interactions described may play a role in maintaining the integrity of circulating enkephalins.     

The determinants of stability in the human prion protein: insights into folding and misfolding from the analysis of the change in the stabilization energy distribution in different conditions

The dynamic evolution of the PrP(C) from its NMR-derived conformation to a beta-sheet-rich, aggregation-prone conformation is studied through all-atom, explicit solvent molecular dynamics in different temperature and pH conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach aimed at identifying the key residues for the stabilization and folding of the protein. It is shown that under native conditions the stabilization energy is concentrated in regions of the helices H1 and H3, whereas under misfolding conditions (low pH, high temperature, or mutations in selected sites) it is spread out over helix H2. Misfolding appears to be a rearrangement of the chain that disrupts most of the native secondary structure of the protein, producing some beta-rich conformations with an energy distribution similar to that of the native state.