scholarly journals In Vitro Modulation of Glibenclamide Transport by P-glycoprotein Inhibitory Antidiabetic African Plant Extracts

Planta Medica ◽  
2019 ◽  
Vol 85 (11/12) ◽  
pp. 987-996
Author(s):  
Udoamaka F. Ezuruike ◽  
Elisabetta Chieli ◽  
Jose M. Prieto
Keyword(s):  
Transport Model ◽  
Diabetic Patients ◽  
Diabetes Incidence ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Reference Drug ◽  
P Glycoprotein ◽  
Efflux Ratio ◽  
Syzygium Guineense

AbstractThe rise of diabetes incidence in Nigeria enhances the use of popular remedies that may interact with conventional therapies. The aqueous extracts of 27 popular Nigerian “antidiabetic” plants were tested for their in vitro effects on glutathione levels within HepG2 cells, P-glycoprotein (P-gp)-mediated Rh-123 efflux activity in Caco-2 vincristine-resistant cells, and modulation of glibenclamide transport in Caco-2 monolayers. The extract from Ximenia americana significantly depleted intracellular glutathione at 100 µg/mL similarly to the reference buthionine sulphoximine (p < 0.05). Other 10 extracts raised glutathione levels. Eight extracts inhibiting P-gp efflux in a concentration-dependent manner (p < 0.01) were selected for further evaluation in a bi-directional transport model across Caco-2 monolayers: Annona senegalensis, Bridellia ferruginea, Cassytha filiformis, Daniellia ogea, Khaya ivorensis, Syzygium guineense, Terminalia avicennioides, and X. americana. When interferences in paracellular transport were discarded, only 3 of them may be modulating the efflux ratio of glibenclamide (efflux ratio: 2.65 ± 0.13) in the same manner the reference drug verapamil (efflux ratio: 1.14 ± 0.25, p < 0.01) does: Syzygium guineense (efflux ratio: 1.70 ± 0.23, p < 0.01), Terminalia avicennioides (efflux ratio: 1.80 ± 0.25, p < 0.05), and X. americana (efflux ratio: 1.66 ± 0.10, p < 0.01). HPLC-UV analyses for P-gp inhibitors in these extracts revealed several phenolic compounds such as rutin, gallic acid, and ellagic acid reported to decrease P-gp expression and/or directly modify its function. In conclusion, some popular herbal medicines used by Nigerian diabetic patients are here shown to potentially affect glibenclamide absorption at concentrations that could be reached in the intestinal tract.

Dietary Nucleotide Supplements in Infant Formula Modify the Expression of P-glycoprotein in the Intestinal Epithelium in vitro

2009 ◽  
Vol 79 (56) ◽  
pp. 381-387 ◽  
Author(s):  
Mary Bebawy ◽  
Christine Rasmussen ◽  
Shwetha Sambasivam ◽  
Shisan Bao
Keyword(s):  
Infant Formula ◽  
Dependent Manner ◽  
Drug Bioavailability ◽  
Concentration Dependent Manner ◽  
Glycoprotein P ◽  
Colon Cells ◽  
P Glycoprotein ◽  
Dietary Nucleotides

The effect of dietary nucleotides at concentrations found in supplemented infant formula on P-glycoprotein (P-gp) expression in colon cells was examined. We report that P-gp expression in colon cells was significantly decreased in a time- and concentration-dependent manner. When colon cells were co-cultured with lymphocytes, so as to mimic the involvement of gut-associated lymphoid tissue in normal gut pathophysiology, we observed a reversal of this effect with a demonstrated increase in P-gp expression. These findings have important implications on effects of nucleotide exposure on increasing drug bioavailability, reducing the capacity for xenobiotic efflux, and increasing the risk of inflammatory bowel disease in susceptible infants. Future studies are directed at defining both the mechanisms underlying these findings and effects of dietary nucleotide supplementation in vivo.

scholarly journals Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 303 ◽  
Author(s):  
Jitka Viktorová ◽  
Simona Dobiasová ◽  
Kateřina Řehořová ◽  
David Biedermann ◽  
Kristýna Káňová ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Resistance Modulation

Silychristin A is the second most abundant compound of silymarin. Silymarin complex was previously described as an antioxidant with multidrug resistance modulation activity. Here, the results of a classical biochemical antioxidant assay (ORAC) were compared with a cellular assay evaluating the antioxidant capacity of pure silychristin A and its derivatives (anhydrosilychristin, isosilychristin and 2,3-dehydrosilychristin A). All the tested compounds acted as antioxidants within the cells, but 2,3-dehydro- and anhydro derivatives were almost twice as potent as the other tested compounds. Similar results were obtained in LPS-stimulated macrophages, where 2,3-dehydro- and anhydrosilychristin inhibited NO production nearly twice as efficiently as silychristin A. The inhibition of P-glycoprotein (P-gp) was determined in vitro, and the respective sensitization of doxorubicin-resistant ovarian carcinoma overproducing P-gp was detected. Despite the fact that the inhibition of P-gp was demonstrated in a concentration-dependent manner for each tested compound, the sensitization of the resistant cell line was observed predominantly for silychristin A and 2,3-dehydrosilychristin A. However, anhydrosilychristin and isosilychristin affected the expression of both the P-gp (ABCB1) and ABCG2 genes. This is the first report showing that silychristin A and its 2,3-dehydro-derivative modulate multidrug resistance by the direct inhibition of P-gp, in contrast to anhydrosilychristin and isosilychristin modulating multidrug resistance by downregulating the expression of the dominant transmembrane efflux pumps.

scholarly journals Discovery of Galangin as a Potential DPP-4 Inhibitor That Improves Insulin-Stimulated Skeletal Muscle Glucose Uptake: A Combinational Therapy for Diabetes

2019 ◽  
Vol 20 (5) ◽  
pp. 1228 ◽  
Author(s):  
Poonam Kalhotra ◽  
Veera Chittepu ◽  
Guillermo Osorio-Revilla ◽  
Tzayhri Gallardo-Velázquez
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Side Effects ◽  
Therapeutic Drug ◽  
Diabetic Patients ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Glucose Levels ◽  
Muscle Health

Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of −24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the proliferation of rat L6 skeletal muscle cells. The combination of galangin with insulin benefits regulation of glucose levels significantly in comparison to galangin alone (p < 0.05). These findings suggest the beneficial effect of the use of galangin, both alone or in combination with insulin, to reduce glucose levels and improve skeletal muscle health in diabetes mellitus.

scholarly journals Evaluation of the anthelmintic properties of a traditional remedy based on a mixture of red algae using an in vitro assay on gastrointestinal nematodes of donkeys

2021 ◽  
Vol 4 (1) ◽  
pp. 1-7
Author(s):  
Michela Maestrini ◽  
◽  
Marcelo Beltrão Molento ◽  
Simone Mancini ◽  
Francesco Saverio Robustelli della Cuna ◽  
...  
Keyword(s):  
Red Algae ◽  
Gastrointestinal Nematode ◽  
Gastrointestinal Nematodes ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Egg Hatch ◽  
Vitro Assay ◽  
Reference Drug ◽  
Negative Controls

The anthelmintic properties and composition of an Italian traditional anthelmintic remedy based on a red algae mixture (RAE) was assessed using the egg hatch test (EHT). The ability of different dilutions \((1.0, 5.0, 50, or 100%)\) of RAE was determined and compared with the positive and negative controls against gastrointestinal nematode (GIN) of donkeys. The experiment was performed in triplicate. Data were analysed using the ANOVA and Tukey test. In the mixture, Palisada tenerrima, Laurencia intricata and Laurencia spp. red algae were identified. The \(100%\) RAE was able to totally inhibit the egg hatch, showing an efficacy comparable \((P < 0.05)\) to that of the reference drug \((98.7%)\). An egg hatch reduction of \(89.5, 43.7\), and \(23.4%\) was observed at \(50, 5\) and \(1%\) dilutions, respectively. In conclusion, RAE was able to inhibit the egg hatch of GIN of donkeys in a concentration-dependent manner with a correlation coefficient \((R2)\) of \(0.968\), corroborating with its anthelmintic effect.

scholarly journals In Vitro Anthelmintic Activity of Saponins from Medicago spp. Against Sheep Gastrointestinal Nematodes

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 242 ◽  
Author(s):  
Michela Maestrini ◽  
Aldo Tava ◽  
Simone Mancini ◽  
Doriana Tedesco ◽  
Stefania Perrucci
Keyword(s):  
Small Ruminants ◽  
Anthelmintic Activity ◽  
Gastrointestinal Nematodes ◽  
Animal Origin ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Reference Drug ◽  
Synthetic Drugs

Gastrointestinal strongyle nematodes (GIS) are included among the most important parasites of small ruminants. The widespread drug resistance and drug residues in products of animal origin have increased the interest in the search for natural compounds with anthelmintic activity as a valid alternative to current synthetic drugs. The aim of the present investigation was to test the ‘in vitro’ anthelmintic activity of saponins and prosapogenins from different Medicago species, selected for their importance as a forage crop worldwide for animal feeding. From these plants, saponin mixtures were extracted, purified and used at scalar concentrations to evaluate their anthelmintic activities against sheep gastrointestinal strongyles (GISs), by the egg hatch test. Treated and untreated controls were used as the comparison. Data were statistically analyzed, and EC50 and EC90 were also calculated. All saponins and prosapogenins showed inhibiting effects on GIS eggs in a concentration-dependent manner. At higher concentrations, most of them showed an efficacy comparable to the reference drug (Thiabendazole 3 µg/mL) (P < 0.001). With 1.72 mg/mL EC50 and 3.84 mg/mL EC90, saponin from M. polymorpha cultivars Anglona was the most active. Obtained results encourage further studies aimed at evaluating the efficacy ‘in vivo’ of saponins which resulted as most effective ‘in vitro’ in this study.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

2020 ◽  
Vol 16 (3) ◽  
pp. 358-362
Author(s):  
Renan S. Teixeira ◽  
Paulo H.D. Carvalho ◽  
Jair A.K. Aguiar ◽  
Valquíria P. Medeiros ◽  
Ademar A. Da Silva Filho ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Crude Extract ◽  
Hepg2 Cells ◽  
Liver Carcinoma ◽  
Adhesion Assay ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Arctium Lappa ◽  
Nih 3T3

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.

scholarly journals Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

2021 ◽  
Vol 22 (13) ◽  
pp. 6785
Author(s):  
Valeria Sogos ◽  
Paola Caria ◽  
Clara Porcedda ◽  
Rafaela Mostallino ◽  
Franca Piras ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Concentration Dependent Manner ◽  
Mechanisms Of Toxicity ◽  
Neuronal Cell Lines

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

scholarly journals The Modulation of PCSK9 and LDLR by Supercritical CO2 Extracts of Mentha longifolia and Isolated Piperitone Oxide, an In Vitro Study

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3886
Author(s):  
Stefania Sut ◽  
Irene Ferrarese ◽  
Maria Giovanna Lupo ◽  
Nicola De Zordi ◽  
Elisa Tripicchio ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Density Lipoprotein ◽  
In Vitro Study ◽  
Volatile Constituent ◽  
Dependent Manner ◽  
Human Hepatoma Cell ◽  
Concentration Dependent Manner

In the present study the ability of supercritical carbon dioxide (SCO2) extracts of M. longifolia L. leaves to modulate low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression was evaluated in cultured human hepatoma cell lines Huh7 and HepG2. Two SCO2 extracts, one oil (ML-SCO2) and a semisolid (MW-SCO2), were subjected to detailed chemical characterization by mono- and bidimensional nuclear magnetic resonance (1D, 2D-NMR), gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS). Chemical analysis revealed significant amounts of fatty acids, phytosterols and terpenoids. ML-SCO2 was able to induce LDLR expression at a dose of 60 µg/mL in HuH7 and HepG2 cell lines. Furthermore, ML-SCO2 reduced PCSK9 secretion in a concentration-dependent manner in both cell lines. Piperitone oxide, the most abundant compound of the volatile constituent of ML-SCO2 (27% w/w), was isolated and tested for the same targets, showing a very effective reduction of PCSK9 expression. The overall results revealed the opportunity to obtain a new nutraceutical ingredient with a high amount of phytosterols and terpenoids using the SCO2 extraction of M. longifolia L., a very well-known botanical species used as food. Furthermore, for the first time we report the high activity of piperitone oxide in the reduction of PCSK9 expression.

Sign in / Sign up

Export Citation Format

Share Document