ChemInform Abstract: Serotonin Derivatives as Inhibitors of β-Secretase (BACE1).

ChemInform ◽  
2011 ◽  
Vol 42 (31) ◽  
pp. no-no ◽  
Author(s):  
T. Takahashi ◽  
M. Miyazawa
2019 ◽  
Vol 47 (02) ◽  
pp. 369-383 ◽  
Author(s):  
Chan Hum Park ◽  
Ah Young Lee ◽  
Ji Hyun Kim ◽  
Su Hui Seong ◽  
Eun Ju Cho ◽  
...  

This study examined whether serotonin and two of its derivatives, [Formula: see text]-feruloylserotonin and [Formula: see text]-([Formula: see text]-coumaroyl) serotonin, have a renoprotective effect in a mouse model of cisplatin-induced acute renal failure. Cisplatin (20[Formula: see text]mg/kg body weight) was administered by intraperitoneal injection to male BALB/c mice that had received oral serotonin, [Formula: see text]-feruloylserotonin or [Formula: see text]-([Formula: see text]-coumaroyl) serotonin (7.5[Formula: see text]mg/kg body weight per day) during the preceding 2 days. At 3 days after the cisplatin injection, serum and renal biochemical factors, oxidative stress, inflammation and apoptosis-related protein expression were evaluated, and histological examinations were performed. Cisplatin caused reduction in body weight and an increase in kidney weight; however, [Formula: see text]-([Formula: see text]-coumaroyl) serotonin and [Formula: see text]-feruloylserotonin attenuated these effects. Moreover, the serotonin derivatives significantly decreased serum urea nitrogen and creatinine levels. They also significantly reduced the level of reactive oxygen species and upregulated the expression of glutathione peroxidase in the kidney. Furthermore, the serotonin derivatives improved the abnormal expression of mitogen-activated protein kinases activation-dependent inflammation- and apoptosis-related protein and caused less renal damage. These results provide important evidence that [Formula: see text]-([Formula: see text]-coumaroyl) serotonin and [Formula: see text]-feruloylserotonin exert a pleiotropic effect on several parameters related to oxidative stress, inflammation and apoptosis. The derivatives also have a renoprotective effect in cisplatin-treated mice; however, this effect is higher with [Formula: see text]-([Formula: see text]-coumaroyl) serotonin.


1988 ◽  
Vol 91 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Hans K. Biesalski ◽  
Horst A. Welker ◽  
Rüdiger Thalmann ◽  
Lutz Vollrath

2009 ◽  
Vol 83 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Kiyoon Kang ◽  
Sangkyu Park ◽  
Young Soon Kim ◽  
Sungbeom Lee ◽  
Kyoungwhan Back

2009 ◽  
Vol 102 (2) ◽  
pp. 264-272 ◽  
Author(s):  
Rosaria Piga ◽  
Yuji Naito ◽  
Satoshi Kokura ◽  
Osamu Handa ◽  
Toshikazu Yoshikawa

Previous reports have shown that safflower-seed extract and its major antioxidant constituents, serotonin hydroxycinnamic amides, attenuated atherosclerotic lesion formation in apoE-deficient mice, as well as inflammation and aortic stiffness in human subjects. In the present report, we examined a still unknown cell-based mechanism of serotonin derivatives against the development of atherosclerosis, focusing our attention on their action against the increase of adhesion molecules and the release of chemotactic factors on human aortic endothelial cells, phenomena that represent the key events in the early stages of atherosclerogenesis. Serotonin derivatives N-(p-coumaroyl)serotonin and N-feruloylserotonin exerted an inhibitory effect on short-term high glucose-induced up-regulation of mRNA and protein of adhesion and migration factors, and the consequent adhesion and migration of monocytes to endothelial cells; they inhibited the activation of transcription factors such as NF-κB, and the overproduction of the mitochondrial superoxide by acting as scavengers of the superoxide radical. In addition, serotonin derivative concentration inside the cells and inside the mitochondria was increased in a time-dependent manner. These results identify a mechanism of action of serotonin derivatives against endothelial damage at a cellular level, and underline their benefits against the disorders and complications related to reactive oxygen species.


2008 ◽  
Vol 101 (4) ◽  
pp. 568-575 ◽  
Author(s):  
Naoto Koyama ◽  
Katsuya Suzuki ◽  
Yasushi Furukawa ◽  
Harumi Arisaka ◽  
Tetsuya Seki ◽  
...  

We previously demonstrated that safflower seed extract (SSE) and its major antioxidant constituents, serotonin hydroxycinnamic acid amides, suppressed LDL oxidation in vitro, decreased plasma autoantibody titres to oxidized LDL and attenuated atherosclerotic lesion formation in apoE-deficient mice. In this report, we examined whether SSE, rich in serotonin derivatives, could affect markers of oxidative stress, inflammation and aortic stiffness in healthy human subjects. Twenty Japanese male volunteers were studied at baseline, after 2·1 g SSE supplementation daily (providing 290 mg serotonin derivatives/d) for 4 weeks, and after a 4-week washout period. Significant reductions in circulating oxidized LDL, autoantibody titres to malondialdehyde-modified LDL, the soluble form of vascular cell adhesion molecule-1 (sVCAM-1), and urinary 8-isoprostane were observed after a 4-week intervention. Although there were no statistically significant differences in blood pressure or brachial–ankle pulse wave velocity (baPWV), an index of arterial stiffness, baPWV was lower than baseline in eleven of twenty subjects and was accompanied by a reduction in blood pressure. Statistically significant negative correlations were observed between the extent of initial cardiovascular risk markers (autoantibody titres, 8-isoprostane, sVCAM-1 and baPWV) and the effect of intervention. This suggested that individuals with elevated oxidative stress, inflammation, and/or arterial stiffness may receive more benefit from SSE supplementation.


Cephalalgia ◽  
1992 ◽  
Vol 12 (4) ◽  
pp. 187-196 ◽  
Author(s):  
Pramod R Saxena ◽  
Michel D Ferrari

After the synthetic serotonin 5-hydroxytryptamine (5-HT) became available in the early 1950s, attempts were soon under way to study the nature of 5-HT receptors. Using the guinea-pig isolated ileum, Gaddum and Picarelli (1957) suggested that 5-HT-induced contractions were mediated by a morphine-sensitive “M” receptor located on the parasympathetic ganglion and a dibenzyline-sensitive “D” receptor located on the smooth muscle. Though this classification was used during the next three decades, it was realized that some effects of serotonin, for example vasoconstriction within the carotid vascular bed, were not mediated by either “M” or “D” receptors. When radioligand binding studies led to the identification of 5-HT1 and 5-HT2 “receptors” in the rat brain membranes, it became increasingly apparent that the two receptor classifications were not identical. Thus, a new framework for serotonin receptor nomenclature and classification was proposed: 5-HT 1 -like (5-HT 1), 5-HT 2 (formerly “D”) and 5-HT 3 (formerly “M”) receptors. At the present time, several subtypes of 5-HT 1 receptors as well as a 5-HT 4 receptor are also recognized. As the serotonin receptor classification was emerging to indicate that carotid vasoconstriction by serotonin is mediated by a subtype of 5-HT 1 receptors, on the migraine front it was being suggested that the disease is associated with vasodilatation within the cranial extracerebral circulation and deranged serotonin metabolism and that certain antimigraine drugs caused a selective carotid vasoconstriction, probably via serotonin receptors. Therefore, Humphrey and colleagues conceived that synthesis of serotonin derivatives may lead to a compound that would elicit highly selective carotid vasoconstriction and abort migraine attacks. Indeed, via the synthesis of 5-carboxamidotryptamine and AH25086, sumatriptan was designed. The drug acts as an agonist at the vasoconstrictor 5-HT 1 receptor subtype and has proved highly effective in the therapy of migraine attacks.


1986 ◽  
Vol 101 (4) ◽  
pp. 415-418
Author(s):  
G. N. Kryzhanovskii ◽  
N. G. Lutsenko ◽  
V. N. Grafova ◽  
E. I. Danilova ◽  
V. K. Lutsenko ◽  
...  

Author(s):  
Prof. Byunggook Kim ◽  
Dr. Hye-Eun Kim ◽  
Ms. Hyejoung Cho ◽  
Prof. Okjoon Kim

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