酸樱桃果实有效成分及药理作用的研究

酸樱桃果实营养丰富、均衡,含有大量的维生素(VA,VB,VC)和矿物质(K,Ca,Fe),而糖类、脂肪、热量的含量较低;尤其富含花青素、各种花色苷、褪黑激素、槲皮素、异槲皮素和其他有效成分.大量研究发现它们具有显著的药理作用,如调节睡眠、清除自由基、抗氧化作用、抗炎、镇痛、抗癌、预防心血管疾病、降低血糖、延缓衰老等.因此,对酸樱桃果实有效成分及药理作用进行了研究.     

Development of post-hatching melatonin rhythm in zebra finches (Poephila guttata)

We examined levels of melatonin in the pineal, eyes and plasma over a 24 h period during development in the altricial zebra finch. Beginning as early as 2 days after hatching there was a distinct 24 h rhythm in melatonin in the pineal and plasma. Beginning at day seven after hatching there was also a 24 h rhythm present in the eyes. In the pineal and eyes the amplitude of the 24 h rhythm increased with age. In contrast, the amplitude of the plasma melatonin rhythm at 2 days was already within the range of adults and did not increase with age. These results confirm and expand earlier findings in the European starling and parallel those from precocial birds indicating that the circadian system is already competent at or shortly after hatching even in atricial birds.     

Melatonin modulates apomorphine-induced rotational behaviour

Summary Prior melatonin administration (1 and 10 mg/kg b.wt) causes a significant reduction in apomorphine (1 mg/kg b.wt) induced rotational behaviour in both 6-hydroxydopamine and quinolinic acid lesioned rats.     

Neural systems underlying photoperiodic time measurement: A blueprint

Summary This paper briefly reviews the formal properties of the photoperiodic time measurement apparatus of mammals and presents a hypothetical model for the operation of the neural systems responsible for reading and responding to the nocturnal pineal melatonin signal. The primary melatonin readout mechanism is held to be common to all species responsive to melatonin. It seems likely that this mechanism responds to relative changes in the duration and amplitude of the melatonin signal, rather than the absolute levels of melatonin encountered. A series of neural systems which exploit the calendar information provided by the primary readout is envisaged to vary between and within species, depending upon the neuroendocrine response under consideration. Of particular importance is a mechanism for comparing the relative duration of successive melatonin signals. These more complex elements are responsible for phenomena such as the effects of photopheriodic history and photorefractoriness. The brain may be able to encode an accumulated memory of melatonin signals and thereby define longer term intervals within the annual cycle. A series of response elements within the hypothalamus are engaged by the appropriately processed photoperiodic stimuli. For all elements of this model, their anatomical representations are poorly understood or, in certain cases, completely unknown.     

A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production

Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE₂ in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay in PGE₂-diminished IL-2 production. The decrease in IL-2 production after PGE₂ and/or luzindole administration correlated with downregulation in the nuclear receptor RORα. We also highlighted a role of cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE₂ in the RORα expression. Finally, a significant RORα downregulation was observed in T cells permanently transfected with inducible MT₁ antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORα expression, opening a new way to understand melatonin regulation in lymphocyte physiology. Received 23 September 2008; received after revision 19 November 2008; accepted 21 November 2008     

Evaluation of signal transduction pathways mediating the nuclear exclusion of the androgen receptor by melatonin

The intracellular signaling pathways mediating the nuclear exclusion of the androgen receptor (AR) by melatonin were evaluated in PC3 cells stably transfected with the AR. The melatonin-induced nuclear exclusion of the AR by melatonin (100 nM, 3 h) was blocked by LY 83583 (an inhibitor of guanylyl cyclases). 8-Bromo-cGMP (a cell-permeable cGMP analog), mimicked the effect of melatonin, as did ionomycin (a calcium ionophore) and PMA [an activator of protein kinase C (PKC)], and their effects were blocked by GF-109203X (a selective PKC inhibitor). BAPTA (an intracellular calcium chelator) blocked the effects of melatonin and 8-bromo-cGMP but not of PMA. Inhibition or activation of the protein kinase A pathway did not affect basal or melatonin-mediated AR localization. We conclude that the melatonin-mediated rise in cGMP elicits AR nuclear exclusion via a pathway involving increased intracellular calcium and PKC activation. These results define a novel signaling pathway that regulates AR localization and androgen responses in target cells. Received 31 July 2001; received after revision 18 September 2001; accepted 30 October 2001     

光谱法研究葫芦脲对褪黑素的分子识别作用

采用荧光光谱、紫外吸收光谱法研究了葫芦[5]脲、葫芦[6]脲、葫芦[7]脲分别与褪黑素的相互作用,考察了溶液的pH值、常用溶剂等对包合物的形成及荧光强度的影响.实验结果表明,褪黑素与葫芦[7]脲不发生作用,而与葫芦[5]脲和葫芦[6]脲发生相互作用,均形成物质的量比为1:1的稳定的包合物.     

Calmodulin mediates melatonin cytoskeletal effects

In this article, we review the data concerning melatonin interactions with calmodulin. The kinetics of melatonin-calmodulin binding suggest that the hormone modulates cell activity through intracellular binding to the protein at physiological concentration ranges. Melatonin interaction with calmodulin may allow the hormone to modulate rhythmically many cellular functions. Melatonin's effect on tubulin polymerization, and cytoskeletal changes in MDCK and N1E-115 cells cultured with melatonin, suggest that at low concentrations (10^–9 M) cytoskeletal effects are mediated by its antagonism to Ca²⁺-calmodulin. At higher concentrations (10^–5 M), non-specific binding of melatonin to tubulin occurs thus overcoming the specific melatonin antagonism to Ca²⁺-calmodulin. Since the structures of melatonin and calmodulin are phylogenetically well preserved, calmodulin-melatonin interaction probably represents a major mechanism for regulation and synchronization of cell physiology.     

Clinical aspects of the melatonin action: impact of development,aging, and puberty,involvement of melatonin in psychiatric disease and importance of neuroimmunoendocrine interactions

During the last decade we have learned much on physiological changes in the secretion of the pineal hormone melatonin (MLT) in man. Reportedly, there is little or no MLT secreted before age 3 months. Then MLT production commences, becmes circadian, and reaches highest nocturnal levels at the age of 1–3 years. During all of childhood nocturnal peak levles drop progressively by 80% until adult levels are reached. This alteration appears to be the consequence of increasing body size in face of constant MLT production during childhood. The biological significance of this MLT alteration is presently unknown. Because of conceptual considerations, major depressive syndrome (MDS) and seasonal affective disorder (SAD) have been in the focus of pineal research for several years. Although in these disorders alterations in MLT levels could not be substantiated, light therapy, a consequence of this research, was discovered as an effective treatment for SAD and perhaps for MDS. In addition, there is some recent evidence for low MLT levels in schizophrenia. Finally, the potential effect of MLT in neuroimmunoendocrine interactions is presently explored. Reportedly, in vitro studies and animal experiments give evidence for a modulatory role of MLT in the immune response. However, the exact way of this possible action of MLT remains to be clarified. Clinical studies are too scant for a meaningful estimation of MLT's involvement in human neuroimmunoendocrine interactions.     

Melatonin decreases the amplitude of the b-wave of the human electroretinogram

In a double-blind placebo crossover study of 13 healthy volunteers, the pineal hormone melatonin (10 mg) was given at 4 pm, and the electroretinogram measured under conditions of dark and light adaptation. A significant diminution of b-wave amplitude was found under both photopic (=5.4 V, p<0.05) and scotopic conditions (=7.4 V, p<0.01). These data indicate that melatonin may transduce the dark signal at the level of the retina as well as the pineal. Acute administration of melatonin decreases sensitivity to light.