scholarly journals In Vitro and in Vivo Effects of Three Different Mitragyna speciosa Korth Leaf Extracts on Phase II Drug Metabolizing Enzymes—Glutathione Transferases (GSTs)

Molecules ◽  
2010 ◽  
Vol 15 (1) ◽  
pp. 432-441 ◽  
Author(s):  
Juzaili Azizi ◽  
Sabariah Ismail ◽  
Mohd Nizam Mordi ◽  
Surash Ramanathan ◽  
Mohd Ikram Mohd Said ◽  
...  
2018 ◽  
Vol 39 (6) ◽  
pp. 2385
Author(s):  
Maciel Dos Santos Freire ◽  
Carmem Dolores Gonzaga Santos

The genus Meloidogyne includes species of the most common nematodes to affect crops around the world. The species M. enterolobii is notable for affecting and causing serious losses in the production of guava trees and various other economically important crops in Brazil. The aim of this study was to evaluate the susceptibility of 10 plant species to parasitism by M. enterolobii, and the in vitro and in vivo effects of their leaf extracts on the pathogen. Initially seedlings of Solenostemon scutellarioides, Dieffenbachia amoena, Spigelia anthelmia, Plumbago scandens, Ricinus communis, Chenopodium ambrosioides, Azadirachta indica, Morinda citrifolia, Jatropha curcas and Datura stramonium were inoculated with 5,000 eggs of M. enterolobii to evaluate their susceptibility to nematode infection. For the test in vitro, a 5% concentration of the leaf extracts were added to Petri dishes, and 50 J2 of M. enterolobii were placed in each dish. After 48 hours incubation, the juveniles were evaluated for motility and mortality in the extracts. For the test in vivo, leaf extracts were used at the same concentration, however with only the seven most-promising in vitro species. This assay included the following sequence: inoculation of 5,000 eggs in autoclaved and moist soil contained in 1L pots; application of 30 ml of extract to the soil after 24 hours; transplanting of ‘Santa Clara’ tomato seedlings the following day; and reapplying the extract after 7 and 14 days. The results were evaluated 45 days after nematode inoculation. It was seen that the species D. amoena, R. communis, A. indica, M. citrifolia, J. curcas and D. stramonium displayed highly resistant behaviour; S. anthelmia, P. scandens and C. ambrosioides were very resistant, whereas S. scutelarioides was susceptible to the nematode. With the in vitro test, extracts from seven of the 10 species caused 70.4% to 97.4% J2 mortality. Applying the best leaf extracts to the soil was efficient in reducing M. enterolobii infestation in roots of the tomato.


2008 ◽  
Vol 36 (4) ◽  
pp. 702-714 ◽  
Author(s):  
Lysiane Richert ◽  
Gregor Tuschl ◽  
Catherine Viollon-Abadie ◽  
Nadège Blanchard ◽  
Alexandre Bonet ◽  
...  

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Jennifer E. Speer ◽  
Yuli Wang ◽  
John K. Fallon ◽  
Philip C. Smith ◽  
Nancy L. Allbritton

Abstract Background The intestinal epithelium is a major site of drug metabolism in the human body, possessing enterocytes that house brush border enzymes and phase I and II drug metabolizing enzymes (DMEs). The enterocytes are supported by a porous extracellular matrix (ECM) that enables proper cell adhesion and function of brush border enzymes, such as alkaline phosphatase (ALP) and alanyl aminopeptidase (AAP), phase I DMEs that convert a parent drug to a more polar metabolite by introducing or unmasking a functional group, and phase II DMEs that form a covalent conjugate between a functional group on the parent compound or sequential metabolism of phase I metabolite. In our effort to develop an in vitro intestinal epithelium model, we investigate the impact of two previously described simple and customizable scaffolding systems, a gradient cross-linked scaffold and a conventional scaffold, on the ability of intestinal epithelial cells to produce drug metabolizing proteins as well as to metabolize exogenously added compounds. While the scaffolding systems possess a range of differences, they are most distinguished by their stiffness with the gradient cross-linked scaffold possessing a stiffness similar to that found in the in vivo intestine, while the conventional scaffold possesses a stiffness several orders of magnitude greater than that found in vivo. Results The monolayers on the gradient cross-linked scaffold expressed CYP3A4, UGTs 2B17, 1A1 and 1A10, and CES2 proteins at a level similar to that in fresh crypts/villi. The monolayers on the conventional scaffold expressed similar levels of CYP3A4 and UGTs 1A1 and 1A10 DMEs to that found in fresh crypts/villi but significantly decreased expression of UGT2B17 and CES2 proteins. The activity of CYP3A4 and UGTs 1A1 and 1A10 was inducible in cells on the gradient cross-linked scaffold when the cells were treated with known inducers, whereas the CYP3A4 and UGT activities were not inducible in cells grown on the conventional scaffold. Both monolayers demonstrate esterase activity but the activity measured in cells on the conventional scaffold could not be inhibited with a known CES2 inhibitor. Both monolayer culture systems displayed similar ALP and AAP brush border enzyme activity. When cells on the conventional scaffold were incubated with a yes-associated protein (YAP) inhibitor, CYP3A4 activity was greatly enhanced suggesting that mechano-transduction signaling can modulate drug metabolizing enzymes. Conclusions The use of a cross-linked hydrogel scaffold for expansion and differentiation of primary human intestinal stem cells dramatically impacts the induction of CYP3A4 and maintenance of UGT and CES drug metabolizing enzymes in vitro making this a superior substrate for enterocyte culture in DME studies. This work highlights the influence of mechanical properties of the culture substrate on protein expression and the activity of drug metabolizing enzymes as a critical factor in developing accurate assay protocols for pharmacokinetic studies using primary intestinal cells. Graphical abstract


Molecules ◽  
2010 ◽  
Vol 15 (5) ◽  
pp. 3378-3390 ◽  
Author(s):  
Biljana Kaurinovic ◽  
Mira Popovic ◽  
Sanja Vlaisavljevic

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