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Chamomile infusions inhibit proteases involved in gastric inflammation
No full textChamomile, prepared with dried flowers from Matricaria recutita L., is one of the most commonly consumed herbal tea. The drug is used for the treatment of gastrointestinal complaints (minor spasms, epigastric distensions, gastritis and gastric inflammation). Several classes of bio-active compounds have been identified in the extracts of chamomile including phenolic acids, coumarins, and flavonoids such as the glycosides of apigenin, quercetin, patuletin, luteolin and several derivatives.
Several studies showed that chamomile infusions possess a protective effect on gastritis and gastric ulcer, but the mechanisms involved in this effect are not completely established. Matrix metalloproteinases (MMPs) and neutrophils elastase (NE) are proteases that degrade extracellular matrix in physiological and pathological conditions. Since MMP-9 and NE are involved in gastric inflammation, the aim of this work was the evaluation of the effects of chamomile infusions of dried capitula (CFI) and sifted (SFI) flowers on MMP-9 and NE, and the identification of the compounds responsible for the observed effect. Each infusion was analyzed by LC-MS/MS in order to verify whether compositional differences affected biological activity.
Analysis of CFI and SFI by LC-MS showed a complex profile. The compounds unequivocally identified by LC-MS/MS were the flavonoids apigenin-7-O-glucoside (api7glu), luteolin-7-O-glucoside (lut7glu), patuletin-7-O-glucoside (pat7glu) and hyperoside (hyp). Api7glu was more abundant in CFI than in SFI whereas the opposite was for lut7glu (5.2 μg/ml vs 8.1 μg/ml). Pat7glu was the most abundant in both the infusions, whereas Hyp was the lowest.
CFI and SFI inhibited enzymatic activity of MMP-9 catalytic domain in a concentration-dependent manner. At 1500 microg/ml the inhibition was 28 % and 55 % for CFI and SFI, respectively. Api7glu and lut7glu (10 μM) showed an inhibitory activity of 40% and 30%, respectively, demonstrating their contribute to the effect of the infusions. The inhibitory effect of CFI and SFI was confirmed on MMP-9 released by human adenocarcinoma cells (AGS cells). CFI was able to inhibit MMP-9 secretion from AGS cells (85% at 1500 microg/ml). The inhibitory effect of the infusions on NE was also tested. Concentration-response curves were performed and IC50 of CFI and SFI on NE were 369.2 microg/ml and 536.7 microg/ml, respectively. The individual compounds that showed an inhibitory effect on NE activity were api7glu (IC50 74.3 microM), lut7glu (IC50 8.6 microM), pat7glu (IC50 10.4 microM), and chlorogenic acid (IC50 31.3 microM).
In conclusion, the present study shows some biochemical mechanism of action for the effect of chamomile infusions and supports the use of chamomile in the treatment of gastrointestinal inflammation
Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase
No full textThe aim of the present study was to confirm that olive oil phenols reduce human platelet aggregability and to verify the hypothesis that cAMP- and cGMP- phosphodiesterases (PDE) could be one of the targets of the biological effect. Four extracts from oils characterized by a high phenol content (HPE), and low phenol levels (LPE) were prepared and analyzed quali- and quantitatively by HPLC-UV and electrospray ionization - MS/MS. Human washed platelets stimulated with thrombin were used for the aggregation assay. Human platelet cAMP-PDE and recombinant PDE5A1 were used as enzyme source. Platelet aggregation and enzyme activity were assayed in the presence of HPE, LPE and individual phenols. The phenol content of HPE ranged between 250 and 500 mg/kg, whereas the LPE content was 46 mg/kg. The compounds identified were hydroxytyrosol (HT), tyrosol (TY), oleuropein aglycone (OleA) and the flavonoids quercetin (QU), luteolin (LU) and apigenin (AP). OleA was the most abundant phenol (range 23.3 to 37.7 %) and LU was the most abundant flavonoid in the extracts. Oil extracts inhibited platelet aggregation with an 50% inhibitory concentration interval of 1.23 -11.2 μg/ml. The inhibitory effect of individual compounds (10 μ m) including homovanillyl alcohol (HVA) followed this order: OleA > LU > HT = TY = QU = HVA, while AP was inactive. All the extracts inhibited cAMP-PDE, while no significant inhibition of PDE5A1 (50 μg/ml) was observed. All the flavonoids and OleA inhibited cAMP-PDE, whereas HT, TY, HVA (100 μm) were inactive. Olive oil extracts and part of its phenolic constituents inhibit platelet aggregation; cAMP-PDE inhibition is one mechanism through which olive oil phenols inhibit platelet aggregation
Inflammatory process and virgin olive oil phenols : modulation of platelet aggregation and metalloprotease-9 expression in monocytes
No full textThe effect of diabetes on neuroactive steroid levels in central and peripheral nervous system
No full textInhibition of human cAMP-phosphodiesterase as a mechanism of the spasmolytic effect of Matricaria recutita L.
No full textMechanisms underlying the spasmolytic activity of chamomile still remain unclear. Inhibition of cAMP-and cGMP-phosphodiesterases (PDE) is one of the mechanisms operated by spasmolytic drugs. In this study, the effect of chamomile on PDE was investigated. Human platelet cAMP-PDE and recombinant PDE5A1 were assayed in the presence of infusions prepared from sifted flowers and capitula. LC-ESI-MS/MS analysis showed different compositions in infusions made with sifted flowers and capitula. Chamomile inhibited cAMP-PDE activity (IC 50 = 17.9-40.5 μg/mL), while CGMP-PDE5 was less affected (-15% at 50 μg/mL). Among the individual compounds tested, only flavonoids showed an inhibitory effect (IC50 = 1.3-14.9 μM), contributing to around 39% of the infusion inhibition; other compounds responsible for cAMP-PDE inhibition still remain unknown. Although experimental evidence supporting the use of chamomile for gastrointestinal minor spasms dates back to the fifties, cAMP-PDE inhibition as a likely mechanism underlying the spasmolytic activity is reported for the first time
Dihydroprogesterone Increases the Gene Expression of Myelin Basic Protein in Spinal Cord of Diabetic Rats
No full textAlterations in myelin membranes, as well as in the expression of myelin proteins have been reported in experimental models of diabetes. Data here reported show for the first time that the mRNA levels of two isoforms of myelin basic protein (MBP), 18.5 and 21.5 kDa, are decreased in the spinal cord of streptozotocin-treated rats and that treatment with a neuroactive steroid, such as progesterone (P), may counteract this effect. Interestingly, metabolism of progesterone into dihydroprogesterone (DHP) by the enzyme 5 alpha-reductase seems to exert an important role in such an effect. As here demonstrated, 5 alpha-reductase mRNA and DHP levels are reduced by diabetes in spinal cord, but treatment with P, is able to counteract these effects. Moreover, treatment with DHP is able to mimic the effect of P on MBP gene expression. Thus, the effects of P here observed are due to its enzymatic conversion into DHP. Because DHP, like P, interacts with P receptor (PR), the present results may suggest the importance to analyze the effects of PR modulators as tools of therapeutic strategies for diabetic complications occurring in nervous system
Sex differences in neuroactive steroid levels in the nervous system of diabetic and non-diabetic rats
No full textNeuropathy and encephalopathy represent important complications of diabetes. Recent observations obtained in experimental models have suggested that, in male rats, neuroactive steroids are protective agents and that their levels in peripheral (PNS) and central (CNS) nervous system are strongly affected by the disease.
It is interesting to highlight that incidence, progression and severity of diabetic neuropathy and diabetic encephalopathy are different in the two sexes. Consequently, it is important to determine the changes in neuroactive steroid levels in the PNS and the CNS of both males and females. To this aim, we have evaluated the levels of neuroactive steroids such as, pregnenolone, progesterone and its metabolites, testosterone and its metabolites, and dehydroepiandrosterone in different CNS regions (i.e., cerebral cortex, cerebellum and spinal cord) and in the sciatic nerve of control and diabetic (i.e., induced by streptozotocin) male and female rats. Data obtained by liquid chromatography-tandem mass spectrometry indicate that the levels of neuroactive steroids show sex and regional differences in control animals. Streptozotocin-induced diabetes resulted in a strong general decrease in neuroactive steroid levels, in both the PNS and the CNS. In addition, the effects of diabetes on neuroactive steroid levels also show sex and regional differences.
These findings may have strong implications for the development of new sex-oriented therapies for the treatment of diabetic neuropathy and diabetic encephalopathy, based on the use of neuroactive steroids
Chamomile infusions inhibit two proteases involved in gastric inflammation: elastase and metalloprotease-9
No full textChamomile (Chamomilla recutita L., Asteraceae Family) is traditionally used as an herbal remedy for the treatment of gastrointestinal inflammatory diseases and is commercially available in sachets containing either the dried flower-heads (capitula) or sifted flowers. Matrix metalloproteases (MMPs) and neutrophil elastase (NE) are proteases involved in gastric inflammation, and contribute to the degradation of gastric mucosa and to the Helicobacter pylori colonization. This study was undertaken to investigate whether the anti-inflammatory effect of chamomile infusion at gastric level could be ascribed to the inhibition of MMP-9 and elastase.
LC-ESI-MS/MS analysis of flavonoids present in CFI and SFI showed different profiles as regards the concentration of apigenin-7-glu, and luteolin-7-glu. MMP-9 secretion and expression were evaluated in human gastric adenocarcinoma cells (AGS) stimulated by 200 nM PMA; NE activity was measured using a chromogenic substrate. The assays were conducted in the presence of chamomile infusions derived from capitula (CFI) and sifted (SFI) flowers (100-1500 μg/ml). Individual flavonoids occurring in both types of infusions were tested as well at 10 μM. The activity and secretion of MMP-9 was determined by zymography and human elastase activity by spectrophotometric assay. MMP-9 promoter activity was investigated in cells transiently transfected with a plasmid containing the luciferase reporter gene under the control of the MMP-9 promoter.
Both types of infusion inhibited the enzymatic activity (-63% and -43% at 1500 μg/ml, for CFI and SFI respectively), the secretion of MMP-9 (IC50 404 and 348 μg/ml for CFI and SFI respectively), as well as the promoter activity (-50% at 1500 μg/ml). Both CFI and SFI reduced the NF-kB driven transcription in a concentration-dependent manner. Notably, the concentration at which the effect was observed is comparable to that affecting the MMP-9 promoter activity. CFI and SFI inhibited elastase activity in a concentration-dependent manner (IC50s of 369 and 537 μg/ml for CFI and SFI, respectively). All the tested flavonoid-7-glycosides (apigenin, luteolin, patuletin and hyperoside) are active at same extent against the targets under study; therefore their contribution to the overall in vitro effect depends on the concentration of each in the infusion.
In conclusion, the present study provides some experimental evidence that MMP-9 and elastase inhibition could represent a mechanism for the anti-inflammatory activity of chamomile infusion at the gastric level. Other mechanisms, however, may also be concurrent
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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