On the quantitative relations between structure and antiaggregation activity of ω-aryl-ω-oxoalkanoic acids

1986 ◽  
Vol 51 (11) ◽  
pp. 2617-2625 ◽  
Author(s):  
Miroslav Kuchař ◽  
Bohumila Brunová ◽  
Jaroslava Grimová ◽  
Václav Rejholec ◽  
Václav Čepelák
Keyword(s):  
Partition Coefficients ◽  
Dissociation Constants ◽  
Inhibitory Effect ◽  
Partition Chromatography ◽  
Linear Quadratic ◽  
Marked Influence ◽  
Methyl Group ◽  
Retention Characteristics ◽  
Anti Inflammatory

A series of ω-aryl-ω-oxoalkanoic acids, I-IV, has been prepared and investigated for dissociation constants in 80% methylcellosolve, retention characteristics in thin-layer partition chromatography and partition coefficients P in the system octanol-water. Also evaluated were their anti-inflammatory efficacy and inhibitory effect on the platelet aggregation induced by collagen. Analysing the relations between structure and antiaggregation effect, we obtained a non-linear, quadratic dependence of this effect on lipophilicity, the optimum being at log P = 3. The antiaggregation effect increased with shortening the chain between the carbonyl and the carboxyl, and with increasing acidity. It was also diminished by the presence of a methyl group on the interlinking chain. To assess the role of lipophilicity we used the RM values of partition chromatography. The relation between anti-inflammatory efficacy and structure was assessed only qualitatively. In this aspect, too, the nature of the chain between the carbonyl and carboxyl proved to have a marked influence. The anti-inflammatory activity proved considerably enhanced by the presence of another aromatic ring in ω-oxoalkanoic acids derived from biphenyl.

scholarly journals The Anti-Inflammatory Effect of Human Telomerase-Derived Peptide onP. gingivalisLipopolysaccharide-Induced Inflammatory Cytokine Production and Its Mechanism in Human Dental Pulp Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yoo-Jin Ko ◽  
Kil-Young Kwon ◽  
Kee-Yeon Kum ◽  
Woo-Cheol Lee ◽  
Seung-Ho Baek ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Map Kinases ◽  
Inhibitory Effect ◽  
Dental Pulp Cells ◽  
Human Dental Pulp Cells ◽  
Human Dental Pulp ◽  
Pulp Cells ◽  
Anti Inflammatory ◽  
Human Telomerase

Porphyromonas gingivalisis considered with inducing pulpal inflammation and has lipopolysaccharide (LPS) as an inflammatory stimulator. GV1001 peptide has anticancer and anti-inflammation activity due to inhibiting activation of signaling molecules after penetration into the various types of cells. Therefore, this study examined inhibitory effect of GV1001 on dental pulp cells (hDPCs) stimulated byP. gingivalisLPS. The intracellular distribution of GV1001 was analyzed by confocal microscopy. Real-time RT-PCR was performed to determine the expression levels of TNF-αand IL-6 cytokines. The role of signaling by MAP kinases (ERK and p38) was explored using Western blot analysis. The effect of GV1001 peptide on hDPCs viability was measured by MTT assay. GV1001 was predominantly located in hDPC cytoplasm. The peptide inhibitedP. gingivalisLPS-induced TNF-αand IL-6 production in hDPCs without significant cytotoxicity. Furthermore, GV1001 treatment markedly inhibited the phosphorylation of MAP kinases (ERK and p38) in LPS-stimulated hDPCs. GV1001 may preventP. gingivalisLPS-induced inflammation of apical tissue. Also, these findings provide mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability.

scholarly journals Biological and physical approaches on the role of piplartine (piperlongumine) in cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiago Henrique ◽  
Caroline de F. Zanon ◽  
Ana P. Girol ◽  
Ana Carolina Buzzo Stefanini ◽  
Nayara S. de A. Contessoto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Physicochemical Analysis ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Anti Inflammatory ◽  
Mimic Peptide

AbstractChronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

scholarly journals The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 1887-1894 ◽  
Author(s):  
Ping Zhang ◽  
Weilan Pan ◽  
Ann H. Rux ◽  
Bruce S. Sachais ◽  
X. Long Zheng
Keyword(s):  
Von Willebrand Factor ◽  
Dissociation Constants ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cooperative Activity ◽  
Carboxyl Terminal ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract ADAMTS13 cleaves von Willebrand factor (VWF) between Tyr1605 and Met1606 residues at the central A2 subunit. The amino-terminus of ADAMTS13 protease appears to be sufficient to bind and cleave VWF under static and denatured condition. However, the role of the carboxyl-terminus of ADAMTS13 in substrate recognition remains controversial. Present study demonstrates that ADAMTS13 cleaves VWF in a rotation speed– and protease concentration–dependent manner on a mini vortexer. Removal of the CUB domains (delCUB) or truncation after the spacer domain (MDTCS) significantly impairs its ability to cleave VWF under the same condition. ADAMTS13 and delCUB (but not MDTCS) bind VWF under flow with dissociation constants (KD) of about 50 nM and about 274 nM, respectively. The isolated CUB domains are neither sufficient to bind VWF detectably nor capable of inhibiting proteolytic cleavage of VWF by ADAMTS13 under flow. Addition of the TSP1 5-8 (T5-8CUB) or TSP1 2-8 repeats (T2-8CUB) to the CUB domains restores the binding affinity toward VWF and the inhibitory effect on cleavage of VWF by ADAMTS13 under flow. These data demonstrate directly and quantitatively that the cooperative activity between the middle carboxyl-terminal TSP1 repeats and the distal carboxyl-terminal CUB domains may be crucial for recognition and cleavage of VWF under flow.

scholarly journals Current Understanding of IL-37 in Human Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhangci Su ◽  
Xiaoan Tao
Keyword(s):  
Autoimmune Diseases ◽  
Human Health ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Inhibitory Effect ◽  
Protective Effects ◽  
Inflammatory Stimuli ◽  
Health And Disease ◽  
Anti Inflammatory

IL-37 is a recently discovered cytokine in the IL-1 family exerting broad protective effects on inflammatory diseases, autoimmune diseases, and cancer. Immune and non-immune cells produce the IL-37 precursor upon pro-inflammatory stimuli. Intracellularly, caspase-1 cleaves and activates IL-37, and its mature form binds to Smad3; this complex translocates into the nucleus where it suppresses cytokine production, consequently reducing inflammation. Extracellularly, IL-37 forms a complex with IL-18Rα and IL-1R8 (formerly TIR8 or SIGIRR) that transduces anti-inflammatory signals by the suppression of NF-κB and MAPK and the activation of Mer-PTEN-DOK pathways. During inflammation, IL-37 suppresses the expression of several pro-inflammatory cytokine in favor to the expression of the anti-inflammatory ones by the regulation of macrophage polarization, lipid metabolism, inflammasome function, TSLP synthesis and miRNAs function. Moreover, IL-37 not only regulates the innate and acquired immunity, but also improves aging-associated immunosenescence. Furthermore, IL-37 exerts an inhibitory effect on tumor angiogenesis and metastasis, and progression. Finally, IL-37 may have a potential ability to reduce excessive inflammation since it is aberrantly expressed in patients with inflammatory diseases, autoimmune diseases, and cancer, thus, it may be used as a marker for different types of diseases. Therefore, this review provides an updated view of the role of IL-37 in human health and disease, and discusses the potential of IL-37 as a therapeutic target and biomarker in inflammatory diseases, autoimmune diseases, and cancer.

Effect of Dipyridamole on Spontaneous Platelet Aggregation in Whole Blood Decreases with the Time After Venepuncture: Evidence for the Role of ADP

1987 ◽  
Vol 58 (02) ◽  
pp. 744-748 ◽  
Author(s):  
A R Saniabadi ◽  
G D O Lowe ◽  
J C Barbenel ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Correlation Coefficient ◽  
Whole Blood ◽  
Blood Platelet ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Adp Receptor ◽  
Spontaneous Platelet Aggregation

SummarySpontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37° C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 μM at each time interval; (b) 0.5-100 μM at 3 and 30 minutes and (c) 15 μM in combination with 100 μM adenosine, 8 μM 2-chloroadenosine (2ClAd, an ADP receptor blocker) and 50 μM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 μM Dipy and 10 μM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 μM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.

Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man

1995 ◽  
Vol 133 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Ettore C degli Uberti ◽  
Maria R Ambrosio ◽  
Marta Bondanelli ◽  
Giorgio Transforini ◽  
Alberto Valentini ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Subjects ◽  
Sympathetic Nerve Activity ◽  
Heart Rate Response ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Nerve Activity ◽  
Receptor Stimulation

degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Valentini A, Rossi R, Margutti A, Campo M. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. Eur J Endocrinol 1995;133:723–8. ISSN 0804–4643 Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60 min infusion of hGAL (80 pmol·kg−1 · min−1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function. Ettore C degli Uberti, Chair of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy

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