scholarly journals Απομόνωση δραστικών εκχυλισμάτων, τμημάτων των φυτών Abies alba και Viscum album subsp. abietis και μελέτη των επιδράσεών τους στον πολλαπλασιασμό κακοηθών σαρκωματικών κυττάρων και σαρκωμάτων επιμύων

2011 ◽  
Author(s):  
Ιωάννης Ζελοβίτης
Keyword(s):  
Ex Vivo ◽  
Abies Alba ◽  
Viscum Album

Μελετήσαμε τις βιολογικές δράσεις ενός μικτού εκχυλίσματος από τους ιστούς των φυτών Viscum album & Abies alba σε μια σειρά in vitro, in vivo και ex vivo μοντέλων καρκίνου. Ως εκχυλιστικό μέσο χρησιμοποιήσαμε κυρίως την αιθυλική αλκοόλη, αλλά και το υποζέον νερό (95 οC) σε συνδυασμό με τη λειοφυλίωση. Οι νεοπλασματικές σειρές που χρησιμοποιήθηκαν για τα in vitro πειράματα ήταν μια σειρά λειομυοσαρκωματικών κυττάρων (LMS) επίμυος Wistar και η λευχαιμική σειρά L–210. Επίσης χρησιμοποιήθηκε για την μελέτη της κυτταροτοξικότητας των λεμφοκυττάρων ΝΚ η ερυθρολευχαιμική σειρά Κ-562. Τα εκχυλίσματα φυτικών ιστών που μελετήθηκαν ήταν: φύλλων, βλαστών, καρπών (Viscum album) και φύλλων, φλοιού, ξύλου (Abies alba). Τέλος μελετήθηκε ένα μικτό εκχύλισμα των δύο φυτών, τόσο ως προς τη κυτταροτοξικότητά του in vitro, όσο και προς τις αντικαρκινικές και αντικαρκινογόνες του ιδιότητες in vivo. Ακόμη μελετήθηκε η δράση του μικτού εκχυλίσματος α) επί της κυτταροτοξικής ικανότητας των NK λεμφοκυττάρων του ανθρώπου, εναντίον νεοπλασματικών κυττάρων της σειράς K-562 και LMS κυττάρων επίμυος Wistar. β) Η αντιμεταστατική του δράση σε ένα in vivo μοντέλο μετάστασης με ενδοφλέβια έγχυση LMS κυττάρων και σε ένα in vitro μοντέλο αιματογενούς μεταστατικής διασποράς, περιλαμβάνον τις αλληλεπιδράσεις μεταξύ νεοπλασματικών κυττάρων και αιμοπεταλίων. γ) Η ολική αντιοξειδωτική του ικανότητα, η ικανότητα αναστολής του ενζύμου 5–LOX, η ικανότητα αναστολής της παραγωγής θρομβοξάνης Α2 και προσταγλανδίνης Ε2 από ανθρώπινα αιμοπετάλια, όπως και από καρκινικά κύτταρα. Τα δεδομένα που προέκυψαν μας δείχνουν ότι το μικτό εκχύλισμα από τους ιστούς των δύο φυτών: 1) Εμφανίζει κυτταροτοξικές ιδιότητες εναντίον των LMS κυττάρων του επίμυος Wistar in vitro. 2) Είναι ισχυρά κυτταροτοξικό απέναντι στην L–210. 3) Είναι ισχυρά κυτταροτοξικό απέναντι στα νεοπλασματικά κύτταρα των όγκων που αναπτύσσονται σε επίμυες Wistar είτε μέσω ενοφθαλμισμού LMS κυττάρων, είτε μέσω έγχυσης 3,4–βενζοπυρενίου. 4) Είναι αντικαρκινογόνο καθόσον αναστέλλει σημαντικά την καρκινογόνο δράση του Β[a]Ρ, μειώνοντας το ποσοστό εμφάνισης κακοηθών όγκων, αλλά και αυξάνοντας το προσδόκιμο επιβίωσης των καρκινοπαθών ζώων. 5) Ενισχύει τη κυτταροτοξική δράση των ΝΚs του ανθρώπου εναντίον καρκινικών κυττάρων Κ-562 και LMS κυττάρων ως στόχων. 6) Αναστέλλει τη μεταστατική διαδικασία στο in vivo μοντέλο μετάστασης στον επίμυ Wistar, αλλά και στο in vitro μοντέλο το σχετικό με τη συσσωρευτική δράση των LMS κυττάρων επί των αιμοπεταλίων του ανθρώπου. 7) Αναστέλλει δοσοεξαρτώμενα την 5-LOX in vitro, καθώς και την κυκλοξυγονάση των ανθρώπινων αιμοπεταλίων και των LMS κυττάρων ex vivo και in vitro αντίστοιχα. 8) Παρουσιάζει αξιόλογη ολική αντιοξειδωτική ισχύ. 9) Διαθέτει πολύ χαμηλή χρόνια τοξικότητα.

scholarly journals Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 37
Author(s):  
João V. D. C. Batista ◽  
Ana Paula S. Matos ◽  
Adriana P. Oliveria ◽  
Eduardo Ricci Júnior ◽  
Zaida M. Freitas ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
Abies Alba ◽  
Viscum Album ◽  
Poloxamer 407 ◽  
In Vitro Assays ◽  
In Vitro Toxicity ◽  
Antitumoral Activity ◽  
Clinical Experiments

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch’s t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm2 of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system.

scholarly journals Synergistic Antitumour Properties ofviscumTTin Alveolar Rhabdomyosarcoma

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Rahel Mascha Stammer ◽  
Susann Kleinsimon ◽  
Jana Rolff ◽  
Sebastian Jäger ◽  
Angelika Eggert ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Viscum Album ◽  
Tumour Volume ◽  
Dependent Manner ◽  
Mistletoe Extract ◽  
Antiapoptotic Proteins ◽  
Cytotoxic Compounds ◽  
Induced Apoptosis

Aqueous mistletoe extracts from the European mistletoe (Viscum album) contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised withβ-cyclodextrins. The combination of an aqueous extract (viscum) and a triterpene-containing extract (TT) recreated a whole mistletoe extract (viscumTT). These extracts were tested on rhabdomyosarcoma in vitro, ex vivo, and in vivo with regard to anticancer effects.ViscumandviscumTTinhibited cell proliferation and induced apoptosis effectively in a dose-dependent manner in vitro and ex vivo, whereasTTshowed only moderate inhibitory effects.viscumTTproved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo.viscumTTinduced apoptosis via the extrinsic and intrinsic pathways, evidenced by the loss of mitochondrial membrane potential and activation of CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising the importance of CASP10 inviscumTT-induced apoptosis. Additionally,viscumTTchanged the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis.viscumTTeffectively reduced tumour volume in patient-derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Organische Nitrate und Thrombozytenfunktion

1988 ◽  
Vol 08 (02) ◽  
pp. 90-99 ◽  
Author(s):  
H. Schröder ◽  
K. Schrör
Keyword(s):  
Endothelial Cell ◽  
Angina Pectoris ◽  
Ex Vivo

ZusammenfassungOrganische Nitrate unterschiedlicher chemischer Struktur sowie Nitroprussidnatrium und Molsidomin (bzw. ihre biologisch aktiven Metaboliten) können die (primäre) Aggregation und Sekretion von Humanthrombozyten in vitro und ex vivo hemmen. Eine solche Wirkung wird für Molsidomin (SIN-1) und Nitroprussidnatrium in vitro in Konzentrationen beobachtet, die in der gleichen Größenordnung liegen wie die vasodilatierenden Effekte der Substanzen. Dagegen sind für eine direkte Antiplättchenwirkung organischer Nitrate (Glyzeryltrinitrat, Isosorbiddinitr at, Isosorbidmononitrate, Teopranitol) in vitro Konzentrationen erforderlich, die ca. 100- bis 1000fach höher sind als die Plasmaspiegel der Substanzen nach therapeutischer Dosierung bzw. die Konzentrationen, die isolierte Gefäßstreifen relaxieren. Als gemeinsamer Wirkungsmechanismus der direkten thrombozy-tenfunktionshemmenden und gefäßerweiternden Wirkung all dieser Substanzen kann heute eine Stickoxid-(NO)-vermittelte Stimulation der cGMP-Bildung angenommen werden, das aus organischen Nitraten als »Pro-drug« entsteht. Die Freisetzung von NO, eines »endothelial cell-derived relaxing factors« (EDRF) aus Nitroprussidnatrium und SIN-1 erfolgt spontan. Dagegen erfordert die Freisetzung von NO aus organischen Nitraten einen enzymatischen Stoffwechselweg, der in isolierten Thrombozyten nicht vorhanden ist. Eine Antiplättchenwirkung organischer Nitrate in vivo bzw. ex vivo wird daher über die Stimulation eines endothelialen, thrombozyteninhibitorischen Faktors erklärt. Hierbei sind Prostazyklin sowie ein bisher unbekannter Endothel-zellfaktor neben einer synergistischen Wirkung organischer Nitrate mit endogenem Prostazyklin in Diskussion. Eine thrombozytenfunktionshemmen-de Wirkung organischer Nitrate könnte in Kombination mit ihren hämody-namischen Effekten auch für die an-tianginöse Wirkung in der Klinik bedeutsam sein, insbesondere zur Verhinderung vasospastischer Zustände bei der instabilen Angina pectoris.

Repurposing N,N-Dimethylacetamide (DMA), a Pharmaceutical Excipient, as a Prototype Novel Anti-inflammatory Agent for the Prevention and/or Treatment of Preterm Birth

2018 ◽  
Vol 24 (9) ◽  
pp. 989-992 ◽  
Author(s):  
Samir Gorasiya ◽  
Juliet Mushi ◽  
Ryan Pekson ◽  
Sabesan Yoganathan ◽  
Sandra E. Reznik
Keyword(s):  
Preterm Birth ◽  
Ex Vivo ◽  
The United States ◽  
Occurrence Rate ◽  
Pharmaceutical Excipient ◽  
Ongoing Work ◽  
Exciting Line ◽  
Pregnant Mice

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide. Inflammation has been identified as the most common cause of PTB, but effective pharmacotherapy has yet to be developed to prevent inflammation driven PTB. Our group has discovered that N,N-dimethylacetamide (DMA), a readily available solvent commonly used as a pharmaceutical excipient, rescues lipopolysaccharide (LPS)-induced timed pregnant mice from PTB. Methods: We have used in vivo, ex vivo and in vitro approaches to investigate this compound further. Results: Interestingly, we found that DMA suppresses cytokine secretion by inhibiting nuclear factor-kappa B (NF-κB). In ongoing work in this exciting line of investigation, we are currently investigating structural analogs of DMA, some of them novel, to optimize this approach focused on the inflammation associated with PTB. Conclusion: Successful development of pharmacotherapy for the prevention of PTB rests upon the pursuit of multiple strategies to solve this important clinical challenge.

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