Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

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Anti-malarial Activity of Isoquinoline Alkaloids from the Stem Bark of Actinodaphne macrophylla

Seven isoquinoline alkaloids isolated from the bark of Actinodaphne macrophylla in this study demonstrated in vitro antiplasmodial activities against Plasmodium falciparum 3D7 with IC50 values of 0.08 μM, 0.05 μM, 1.18 μM, 3.11 μM, 0.65 μM, 0.26 μM, and 1.38 μM for cycleanine, 10-demethylxylopinine, reticuline, laurotetanine, bicuculine, α-hydrastine and anolobine, respectively, which are comparable with the reference standard, chloroquine. 10-Demethylxylopinine was found to be the most active of these compounds

Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC50 = 60.17 µM) and BChE (IC50 = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes

New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity

Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations

Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities

Annona muricata is a member of the Annonaceae family and is a fruit tree with a long history of traditional use. A. muricata, also known as soursop, graviola and guanabana, is an evergreen plant that is mostly distributed in tropical and subtropical regions of the world. The fruits of A. muricata are extensively used to prepare syrups, candies, beverages, ice creams and shakes. A wide array of ethnomedicinal activities is contributed to different parts of A. muricata, and indigenous communities in Africa and South America extensively use this plant in their folk medicine. Numerous investigations have substantiated these activities, including anticancer, anticonvulsant, anti-arthritic, antiparasitic, antimalarial, hepatoprotective and antidiabetic activities. Phytochemical studies reveal that annonaceous acetogenins are the major constituents of A. muricata. More than 100 annonaceous acetogenins have been isolated from leaves, barks, seeds, roots and fruits of A. muricata. In view of the immense studies on A. muricata, this review strives to unite available information regarding its phytochemistry, traditional uses and biological activities

Tanacetum polycephalum (L.) Schultz-Bip. Induces Mitochondrial-Mediated Apoptosis and Inhibits Migration and Invasion in MCF7 Cells

Tanacetum polycephalum (L.) Schultz-Bip (Mokhaleseh) has been traditionally used in the treatment of headaches, migraines, hyperlipidemia and diabetes. The present study aimed to evaluate its anticancer properties and possible mechanism of action using MCF7 as an in vitro model. T. polycephalum leaves were extracted using hexane, chloroform and methanol solvents and the cytotoxicity was evaluated using the MTT assay. Detection of the early apoptotic cells was investigated using acridine orange/propidium iodide staining. An Annexin-V-FITC assay was carried out to observe the phosphatidylserine externalization as a marker for apoptotic cells. High content screening was applied to analyze the cell membrane permeability, nuclear condensation, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed by using caspase-8, caspase-9 and DNA laddering assays. In addition, Bax/Bcl-2 expressions and cell cycle arrest also have been investigated. MTT assay revealed significant cytotoxicity of T. Polycephalum hexane extract (TPHE) on MCF7 cells with the IC50 value of 6.42 ± 0.35 µg/mL. Significant increase in chromatin condensation was also observed via fluorescence analysis. Treatment of MCF7 cells with TPHE encouraged apoptosis through reduction of MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering the cytochrome c leakage from mitochondria to the cytosol. The treated MCF7 cells significantly arrested at G1 phase. The chromatographic analysis elicited that the major active compound in this extract is 8β-hydroxy-4β,15-dihydrozaluzanin C. Taken together, the results presented in this study demonstrated that the hexane extract of T. Polycephalum inhibits the proliferation of MCF7 cells, resulting in the cell cycle arrest and apoptosis, which was explained to be through the mitochondrial pathway

Katamnestische Untersuchungen zur suprakondylären und y-kondylären Humerusfraktur im Kindesalter

Die Arbeit beschäftigt sich mit der suprakondylären und y-kondylären Humerusfraktur im Kindesalter. Die suprakondyläre Humerusfraktur ist die häufigste Ellenbogenfraktur beim Kind, die y-kondyläre Fraktur ist der suprakondylären ähnlich, tritt aber nur selten auf. Es wurden 172 suprakondyläre und 6 y-kondyläre Humerusfrakturen retrospektiv untersucht. Dazu wurden die Daten von 55 ambulant und 123 stationär behandelten Kindern bezüglich Unfallursache, Therapie und Komplikationen ausgewertet. Die Röntgenbilder der stationären Patienten wurden nachbefundet. 32,5% der stationär behandelten Kinder konnten nachuntersucht werden. Die häufigste Unfallursache war ein Sturz aus der Höhe. Im Patientengut waren Frakturen nach Baumann Klassifikation I, II und III zu ähnlichen Teilen vorhanden. Häufigste Behandlungsverfahren waren, ggf. nach geschlossener Reposition, Ruhigstellung in Gipslonguetten oder Blountscher Schlinge, und geschlossene oder offene Reposition und anschließende Fixation mittels Kirschner Drähten. Die häufigsten Komplikationen waren primäre und sekundäre Nervenstörungen, Abweichung der Ellenbogenachse oder Bewegungseinschränkung nach Therapie. 68,5% der nachuntersuchten Patienten hatten ein exzellentes oder gutes Behandlungsergebnis. Die Analyse der Ergebnisse und deren Vergleich mit den Ergebnissen anderer Autoren zeigen Folgendes: Nicht dislozierte Extensionsfrakturen sollten in der Blountschen Schlinge ruhiggestellt werden. Dislozierte Frakturen müssen exakt und schonend, möglichst geschlossen, reponiert werden. Gekreuzte Kirschner Drähte bieten gute Stabilität. Primäre und sekundäre Nervenstörungen haben eine gute Prognose. Radiologische Hilfsmittel wie Baumannwinkel, Rotationsfehlerquotient und Epiphysenachsenwinkel geben nur eine Orientierung bei der Vermeidung von Abweichungen der Ellenbogenachse oder Bewegungseinschränkungen. Y-kondyläre Frakturen mit nur geringer Dislokation der Kondylenfragmente können primär wie suprakondyläre Frakturen behandelt werden.This paper deals with supracondylar and y-condylar humerus fractures in childhood. The supracondylar humerus fracture is the most frequent elbow fracture in children, the y-condylar fracture is similar to the supracondylar one, but occurs only rarely. 172 supracondylar and 6 y-condylar humerus fractures have been analysed retrospectively. For that purpose data of 55 outpatients and 123 in-house treated children have been analysed with regard to the cause of accident, therapy and complications. The radiographs of the in-patients have been revaluated. 32.5% of the in-patients have been seen for follow-up. Most frequent cause of accident was a fall from a height. Within the group of patients, fractures that were classified to Baumann I, II and III occurred to equal rates. The treatments which were used mostly are immobilization in plaster casts or Blount´s loop, after closed reduction if necessary, and closed or open reduction followed by fixation by Kirschner wires. The most frequent complications were primary and secondary nerval disorders, deviation of the axis of the elbow or limitation of elbow function after therapy. 68.5% of the follow-up patients had an excellent or good outcome. The analysis of the results including their comparison to the results of other authors have led to the following conclusion: Nondisplaced extension fractures should be immobilized by Blount`s method. Displaced fractures have to be reduced accurately and sparing, if possible by closed reduction. Crossed Kirschner wires provide a good stability. Primary and secondary nerval disorders have got a good prognosis. Radiological tools like angle of Baumann, rotation error quotient and angle of epiphyseal axis only provide an orientation in avoiding deviation of elbow axis or limitation of elbow function. Y-condylar fractures with only slight dislocation of the condylar fragments can primary be treated like supracondylar fractures

Effects of annomuricin E on LDH leakage formation in HT-29 cells.

<p>Cells were exposed to 0.1% vehicle DMSO (control) and annomuricin E at different concentrations for 24 h. The treated HT-29 cells showed a significant LDH release at 4 to 16 μg/ml concentrations compared with the control. The data represent the means ± SEM of three independent experiments. *<i>P</i><0.05 compared with the control.</p