In Vitro Modulation of Human Foam Cell Formation and Adhesion Molecules Expression by Ginger Extracts Points to Potential Cardiovascular Preventive Agents.

Recent findings from the World Heart Federation (WHF) reported a significant increase in cardiovascular disease (CVD)-related deaths, highlighting the urgent need for effective prevention strategies. Atherosclerosis, a key precursor to CVD, involves the accumulation of low-density lipoprotein (LDL) and its oxidation within the endothelium, leading to inflammation and foam cell formation. Ginger extracts, known for their antioxidative and anti-inflammatory properties, show promise in preventing CVD initiation by inhibiting LDL oxidation and reducing foam cell formation. Our results revealed that the active fractions in ginger extracts had antioxidative effects, particularly fractions D and E. Further research is needed to identify the active compounds in these fractions and understand their mechanisms of action. In this context, microfluidic models could offer insights into the effects of ginger on monocyte recruitment in a more physiologically relevant context. Overall, ginger extracts represent a potential novel treatment for preventing CVD initiation, but additional studies are necessary to identify the active molecules in these fractions.

Evaluation of Tandem Mass Spectrometry Experiments in the Negative Ionization Mode for Phenolamide Regioisomer Characterization.

Phenolamides are abundant specialized metabolites found in nature and consist of hydroxycinnamic acids mono- or polyconjugated with polyamines. Their participation in flower development is well-documented, and their presence in pollen raises the question of their role in pollen/pollinator interactions. The structural characterization of phenolamides is complicated by the presence of positional isomers and stereoisomers. Liquid chromatography coupled to tandem mass spectrometry in the positive ionization mode is becoming very popular in phenolamide structural characterization. However, collision-induced transamidation processes that cause the swapping of side chains have been detected, making it difficult to distinguish regioisomers with this technique. In the present report, we explore the dissociation processes undergone by the [M - H]- ions of spermidine-based phenolamides as model compounds. We describe two original competitive dissociation routes, namely, the phenolate and imidate pathways, to account for the observed fragmentation reactions undergone by collisional activated standard phenolamide anions. Whereas the phenolate pathway is regioselective at the central position for spermidine, the imidate pathway, requiring a deprotonated amide, only occurs at the extremities. Tandem mass spectrometry experiments on negatively charged phenolamide ions may then outperform their positive ionization mode counterparts for the distinction between phenolamide regioisomers and globally for the identification of phenolamides in natural extracts.

Nuclear magnetic resonance relaxometry to monitor chromium (VI) reduction by hydrogen peroxide, ascorbic acid, and aluminum powder.

The reduction of K2 Cr2 O7 solutions by H2 O2 was studied by nuclear magnetic resonance (NMR) relaxometry and UV-vis spectroscopy in HCl/KCl buffer (pH 2), NaCl/glycine/HCl buffer (pH 3), and sodium acetate/acetic acid buffer (pH 4). Because of Cr(III) paramagnetism, 1/T1 and 1/T2 of the solutions increase during the reduction of diamagnetic Cr(VI). This increase is proportional to the produced Cr(III) concentration. Using different initial H2 O2 concentrations, partially reduced Cr(VI) samples were prepared and studied by T1 and T2 relaxometry and by UV-vis spectroscopy. The correlation between the relaxation rates and the concentration of Cr(VI) remaining in the sample, measured by spectroscopy, was excellent. It was possible, thanks to the measurement of T2 , to study the kinetics of the reduction of K2 Cr2 O7 by H2 O2 in the pH 3 and pH 4 buffers. The reduction of Cr(VI) by ascorbic acid was successfully monitored by NMR relaxometry in the pH 2 buffer. The presence of complexing molecules/ions was shown to drastically influence the nuclear magnetic relaxation dispersion profiles of reduced K2 Cr2 O7 solutions: Both relaxation rates are divided by ~5 when citrate or acetate ions are present and by ~3 in the presence of ascorbic acid. Therefore, the comparison of relaxation results obtained in different reaction mixtures must be done carefully. When all the solutions are set to pH 0, which prevents any complexation, the longitudinal and transverse relaxation rates of all samples become comparable. Finally, as a proof of concept for a turbid solution, the kinetics of the reduction of a K2 Cr2 O7 solution by aluminum powder in the pH 2 buffer was successfully monitored.

Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction.

The interaction between SARS-CoV-2 spike RBD and ACE2 proteins is a crucial step for host cell infection by the virus. Without it, the entire virion entrance mechanism is compromised. The aim of this study was to evaluate the capacity of various natural product classes, including flavonoids, anthraquinones, saponins, ivermectin, chloroquine, and erythromycin, to modulate this interaction. To accomplish this, we applied a recently developed a microfluidic diffusional sizing (MDS) technique that allows us to probe protein-protein interactions via measurements of the hydrodynamic radius (Rh) and dissociation constant (KD); the evolution of Rh is monitored in the presence of increasing concentrations of the partner protein (ACE2); and the KD is determined through a binding curve experimental design. In a second time, with the protein partners present in equimolar amounts, the Rh of the protein complex was measured in the presence of different natural products. Five of the nine natural products/extracts tested were found to modulate the formation of the protein complex. A methanol extract of Chenopodium quinoa Willd bitter seed husks (50 µg/mL; bisdesmoside saponins) and the flavonoid naringenin (1 µM) were particularly effective. This rapid selection of effective modulators will allow us to better understand agents that may prevent SARS-CoV-2 infection.

The Xanthophyll Carotenoid Lutein Reduces the Invasive Potential of Pseudomonas aeruginosa and Increases Its Susceptibility to Tobramycin.

Recently, the xanthophyll carotenoid lutein has been qualified as a potential quorum sensing (QS) and biofilm inhibitor against Pseudomonas aeruginosa. To address the potential of this xanthophyll compound as a relevant antivirulence agent, we investigated in depth its impact on the invasion capabilities and aggressiveness of P. aeruginosa PAO1, which rely on the bacterial ability to build and maintain protective barriers, use different types of motilities and release myriad virulence factors, leading to host cell and tissue damages. Our data, obtained on the PAO1 strain, indicate that all-trans lutein (Lut; 22 µM) disrupts biofilm formation and disorganizes established biofilm structure without affecting bacterial viability, while improving the bactericidal activity of tobramycin against biofilm-encapsulated PAO1 cells. Furthermore, this xanthophyll affects PAO1 twitching and swarming motilities while reducing the production of the extracellular virulence factors pyocyanin, elastase and rhamnolipids as well as the expression of the QS-regulated lasB and rhlA genes without inhibiting the QS-independent aceA gene. Interestingly, the expression of the QS regulators rhlR/I and lasR/I is significantly reduced as well as that of the global virulence factor regulator vfr, which is suggested to be a major target of Lut. Finally, an oxidative metabolite of Lut, 3'-dehydrolutein, induces a similar inhibition phenotype. Taken together, lutein-type compounds represent potential agents to control the invasive ability and antibiotic resistance of P. aeruginosa.

Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells.

Cardiovascular diseases (CVD) and cancers are the two main causes of death worldwide. The initiation and progression of atherosclerosis is, in large part, caused by oxidized low-density lipoproteins (oxLDL); interestingly, oxLDL may also play a role in cancer cell metabolism and migration. As oxLDL are generally obtained by tedious ultracentrifugation procedures, "home-made" oxLDL were obtained by (i) applying a purification kit to isolate LDL and VLDL from human plasma; (ii) isolating LDL from VLDL by gel permeation chromatography (GPC); and (iii) oxidating LDL through CuSO4 incubation. On three HPV-positive head and neck cancer cells (HNCC) (93VU-147T, UM-SCC47, and UPCI-SCC154), cell migration was assessed using Boyden chambers, the Wnt/ß-catenin pathway was analyzed by Western Blotting, and the expression of two oxLDL receptors, LOX-1 and CD36, in response to oxLDL exposure, was analysed by immunofluorescence. Our data indicate: (a) a non-significant difference between reference and "home-made" oxLDL; (b) a decreased migration, parallel to an inhibition of the ß-catenin pathway; and (c) an increase of CD36 and LOX-1 expression in all HNCC. In conclusion, we successfully produced oxLDL. Our results demonstrate a decrease in HNCC migration after oxLDL exposure, and an increased expression of LOX-1 and CD36 associated with lipid uptake.

Endogenous Synthesis of Tetrahydroisoquinoline Derivatives from Dietary Factors: Neurotoxicity Assessment on a 3D Neurosphere Culture.

Tetrahydroisoquinoline (THIQ) alkaloids and their derivatives have a structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a well-known neurotoxin. THIQs seem to present a broad range of actions in the brain, critically dependent on their catechol moieties and metabolism. These properties make it reasonable to assume that an acute or chronic exposure to some THIQs might lead to neurodegenerative diseases including essential tremor (ET). We developed a method to search for precursor carbonyl compounds produced during the Maillard reaction in overcooked meats to study their reactivity with endogenous amines and identify the reaction products. Then, we predicted in silico their pharmacokinetic and toxicological properties toward the central nervous system. Finally, their possible neurological effects on a novel in vitro 3D neurosphere model were assessed. The obtained data indicate that meat is an alkaloid precursor, and we identified the alkaloid 1-benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol (1-benz-6,7-diol THIQ) as the condensation product of phenylacetaldehyde with dopamine; in silico study of 1-benz-6,7-diol-THIQ reveals modulation of dopamine receptor D1 and D2; and in vitro study of 1-benz-6,7-diol-THIQ for cytotoxicity and oxidative stress induction does not show any difference after 24 h contact for all tested concentrations. To conclude, our in vitro data do not support an eventual neurotoxic effect for 1-benz-6,7-diol-THIQ.

Effects of Chemopreventive Natural Compounds on the Accuracy of 8-oxo-7,8-dihydro-2'-deoxyguanosine Translesion Synthesis.

Translesion synthesis is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis. Specialized translesion synthesis DNA polymerases pursue replication by inserting a base opposite to this lesion, correctly or incorrectly depending on the lesion nature, involved DNA polymerase(s), sequence context, and still unknown factors. To measure the correct or mutagenic outcome of 8-oxo-7,8-dihydro-2'-deoxyguanosine bypass by translesion synthesis, a primer-extension assay was performed in vitro on a template DNA bearing this lesion in the presence of nuclear proteins extracted from human intestinal epithelial cells (FHs 74 Int cell line); the reaction products were analyzed by both denaturing capillary electrophoresis (to measure the yield of translesion elongation) and pyrosequencing (to determine the identity of the nucleotide inserted in front of the lesion). The influence of 14 natural polyphenols on the correct or mutagenic outcome of translesion synthesis through 8-oxo-7,8-dihydro-2'-deoxyguanosine was then evaluated in 2 experimental conditions by adding the polyphenol either (i) to the reaction mix during the primer extension assay; or (ii) to the culture medium, 24 h before cell harvest and nuclear proteins extraction. Most of the tested polyphenols significantly influenced the outcome of translesion synthesis, either through an error-free (apigenin, baicalein, sakuranetin, and myricetin) or a mutagenic pathway (epicatechin, chalcone, genistein, magnolol, and honokiol).

Characterization of the UDP-glycosyltransferase UGT72 Family in Poplar and Identification of Genes Involved in the Glycosylation of Monolignols.

Monolignols are the building blocks for lignin polymerization in the apoplastic domain. Monolignol biosynthesis, transport, storage, glycosylation, and deglycosylation are the main biological processes partaking in their homeostasis. In Arabidopsis thaliana, members of the uridine diphosphate-dependent glucosyltransferases UGT72E and UGT72B subfamilies have been demonstrated to glycosylate monolignols. Here, the poplar UGT72 family, which is clustered into four groups, was characterized: Group 1 UGT72AZ1 and UGT72AZ2, homologs of Arabidopsis UGT72E1-3, as well as group 4 UGT72B37 and UGT72B39, homologs of Arabidopsis UGT72B1-3, glycosylate monolignols. In addition, promoter-GUS analyses indicated that poplar UGT72 members are expressed within vascular tissues. At the subcellular level, poplar UGT72s belonging to group 1 and group 4 were found to be associated with the nucleus and the endoplasmic reticulum. However, UGT72A2, belonging to group 2, was localized in bodies associated with chloroplasts, as well as possibly in chloroplasts. These results show a partial conservation of substrate recognition between Arabidopsis and poplar homologs, as well as divergent functions between different groups of the UGT72 family, for which the substrates remain unknown.

Hydroxyurea (hydroxycarbamide) genotoxicity in pediatric patients with sickle cell disease.

BACKGROUND: Hydroxyurea (HU) reduces the severity of sickle cell disease (SCD) in children; nevertheless, its long-term safety is an important concern. This paper evaluates HU genotoxicity at dose ≤ 30 mg/kg/day after over 2 years of treatment. PROCEDURE: The study included 76 children: 32 SCD patients treated with HU, 27 SCD patients not treated with HU, and 17 unaffected children. HU patients were classified as good or poor responders according to their clinical response. Comet assay allows the comparison of DNA damage between both groups of patients and unaffected children. Maximal concentration (Cmax ) of HU in plasma was determined after drug administration. RESULTS: Mean values of DNA in the comet tail were 5.13 ± 6.84 for unaffected children, 5.80 ± 7.78 for patients with SCD treated with HU, and 5.61 ± 6.91 for patients with SCD not treated with HU. Significant differences were observed between unaffected children and children with SCD. No difference was evident between comets from SCD patients treated and not treated with HU. In the case of HU, mean DNA in the comet tail was significantly lower in good responders than in poor responders: 5.54 ± 7.77 and 6.69 ± 8.43, respectively. Mean Cmax value on plasma was 39.08 ± 15.65 mg/l; N = 31. CONCLUSIONS: SCD increases, slightly but significantly, DNA damage in lymphocytes from patients with SCD. Patients with SCD treated with HU do not present more nucleoid damage than patients with SCD not treated with HU. Good responders to the HU treatment have significantly less nucleoid damage than poor responders. HU treatment at ≤30 mg/kg/day does not expose patients to a genotoxic plasma concentration.

Impact of Moringa oleifera lam. Leaf powder supplementation versus nutritional counseling on the body mass index and immune response of HIV patients on antiretroviral therapy: a single-blind randomized control trial.

BACKGROUND: To achieve effective antiretroviral therapy (ART) outcomes, adherence to an antiretroviral regimen and a good immunometabolic response are essential. Food insecurity can act as a real barrier to adherence to both of these factors. Many people living with human immunodeficiency virus (PLHIV) treated with ART in the Democratic Republic of the Congo (DRC) are faced with nutritional challenges. A significant proportion are affected by under nutrition, which frequently leads to therapeutic failure. Some HIV care facilities recommend supplementation with Moringa oleifera (M.O.) Lam. leaf powder to combat marginal and major nutritional deficiencies. This study aims to assess the impact of M.O. Lam. leaf powder supplementation compared to nutritional counseling on the nutritional and immune status of PLHIV treated with ART. METHODS: A single-blind randomized control trial was carried out from May to September 2013 at an outpatient clinic for HIV-infected patients in Kinshasa (DRC). Sixty adult patients who were at stable HIV/AIDS clinical staging 2, 3 or 4 according to the World Health Organization (WHO), and were undergoing ART were recruited. After random allocation, 30 patients in the Moringa intervention group (MG) received the M.O. Lam. leaf powder daily over 6 months, and 30 in the control group (CG) received nutritional counseling over the same period. Changes in the body mass index (BMI) were measured monthly and biological parameters were measured upon admission and at the end of the study for the patients in both groups. RESULTS: The two study groups were similar in terms of long-term nutritional exposure, sociodemographic, socioeconomic, clinical, and biological features. At 6 months follow-up, patients in the MG exhibited a significantly greater increase in BMI and albumin levels than those in the CG. The interaction between the sociodemographic, clinical, and biological characteristics of patients in the two groups was not significant, with the exception of professional activity. CONCLUSIONS: Under medical supervision, M.O. Lam. leaf powder supplementation may represent a readily available and effective local solution to improve the nutritional intake and nutritional status of PLHIV undergoing ART. TRIAL REGISTRATION: The study was retrospectively registered in the Pan African Clinical Trial Registry on 15 May 2015, no. PACTR201505001076143.

Hypoglycemic and Antihyperglycemic Activities of Nine Medicinal Herbs Used as Antidiabetic in the Region of Lubumbashi (DR Congo).

The aim of this study was to assess the hypoglycemic and antihyperglycemic activities of nine plants used as antidiabetic treatments in Lubumbashi and its surroundings. Those are Albizia adianthifolia, Azanza garckeana, Cassia occidentalis, Cassia sieberiana, Erythrina abyssinica, Gladiolus klattianus, Rauvolfia caffra, Strychnos spinosa, and Vitex madiensis. Aqueous extracts, obtained by decoction and maceration, were administered (500 mg/kg) per os to guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral glucose tolerance test (OGTT) conditions (glucose, 2 g/kg; follow-up over 210 min). For OGTT experiments, area under the curve of blood glucose levels, maximum glucose concentration (Cmax), and time to reach Cmax (Tmax) were used to compare test groups with the control conditions (glucose group). In hypoglycemic tests, only three species induced significant (p < 0.001) lowering of normal glycemia: A. adianthifolia (33% reduction), C. occidentalis (32%), and V. madiensis (43%); in the same conditions, the positive control glibenclamide (6 mg/kg) induced a blood glucose lowering of 55%. In OGTT conditions, all tested herbs were active, with the highest inhibition of glycemia increases for V. madiensis (62%) and A. adianthifolia (57%), compared with the hyperglycemic inhibition rate of glibenclamide (50%). Oral glucose tolerance test conditions appear as essential to detect the extracts most interesting for clinical use. These data support the use of studied plants for diabetes treatment in traditional Congolese medicine and indicate a good knowledge of tradipraticians in the field. Copyright © 2017 John Wiley & Sons, Ltd.

In vitro Study of Five Herbs Used Against Microbial Infections in Burundi.

The emergence of antimicrobial resistant infectious diseases remains a major threat to worldwide public health, in developed and in developing countries. Therefore, new antimicrobial agents acting by new mechanisms of action are urgently needed. As plants used in traditional medicine may help to overcome these problems, Justicia subsessilis, Platostoma rotundifolium, Pavetta ternifolia, Stomatanthes africanus, and Virectaria major (plants highly cited to be used against microbial infections in traditional Burundian medicine) were studied to assess their traditional use efficacy. We conducted a preliminary phytochemical screening of the extracts, as well as their direct and indirect (effect on antibiotic resistance) antibacterial activity on four bacterial strains (Staphylococcus sp. and Escherichia coli) by broth microdilution methods. All five medicinal plants investigated in this work were found to have direct antibacterial activity against all tested bacterial strains (minimum inhibitory concentration = 62.5-1000 µg/mL) that may support the use of these species in traditional Burundian medicine. Extracts (with no direct antibacterial activity), tested at 200 µg/mL, decreased the MIC values of ß-lactams and aminoglycoside antibiotics by a factor of 2 to 64-fold. These interactions between plant extracts and antibiotics could open an avenue of research against antibiotic resistance. Copyright © 2017 John Wiley & Sons, Ltd.

Synthesis of Quercetin-imprinted Polymer Spherical Particles with Improved Ability to Capture Quercetin Analogues.

INTRODUCTION: Molecularly imprinted polymers (MIPs) are composed of specific cavities able to selectively recognise a template molecule. Used as chromatographic sorbents, MIPs may not trap related structures due to the high rigidity of their cross-linking. OBJECTIVE: To improve the capture of quercetin analogues by modulating the synthesis strategy for a quercetin-imprinted polymer (Qu MIP). METHODOLOGY: An additional comonomer bearing a short oligoethylene glycol (OEG) unit was used to prepare a Qu MIP that was compared to a traditional one formulated in a similar fashion, but without the OEG-comonomer. The Qu MIPs were prepared in bead form through fluorocarbon suspension polymerisation. After solid phase extraction (SPE) assessment of their imprinted cavities, the MIPs were evaluated by HPLC for their recognition properties towards quercetin and other polyphenols, including flavonoids, phenolic acids and curcumin. The Qu MIPs were finally SPE-tested on a white onion extract. RESULTS: The incorporation of OEG units modulated the selectivity of the Qu MIP by improving the recognition of quercetin related structures (12-61% increase in the imprinting effect for distant analogues). It also allowed limiting or suppressing non-specific hydrophobic interactions (decrease of about 10% in the rate of quercetin retention on the non-imprinted polymer). The SPE application of the MIP to a white onion extract indicates its interest for the selective extraction of quercetin and its analogues. CONCLUSION: The OEG-modified Qu MIP appears to be an attractive tool to discover new drug candidates from natural sources by extracting, amongst interfering compounds, structural analogues of quercetin. Copyright © 2017 John Wiley & Sons, Ltd.

Terpenoids from Platostoma rotundifolium (Briq.) A. J. Paton Alter the Expression of Quorum Sensing-Related Virulence Factors and the Formation of Biofilm in Pseudomonas aeruginosa PAO1.

Platostoma rotundifolium (Briq.) A. J. Paton aerial parts are widely used in Burundi traditional medicine to treat infectious diseases. In order to investigate their probable antibacterial activities, crude extracts from P. rotundifolium were assessed for their bactericidal and anti-virulence properties against an opportunistic bacterial model, Pseudomonas aeruginosa PAO1. Whereas none of the tested extracts exert bacteriostatic and/or bactericidal proprieties, the ethyl acetate and dichloromethane extracts exhibit anti-virulence properties against Pseudomonas aeruginosa PAO1 characterized by an alteration in quorum sensing gene expression and biofilm formation without affecting bacterial viability. Bioguided fractionation of the ethyl acetate extract led to the isolation of major anti-virulence compounds that were identified from nuclear magnetic resonance and high-resolution molecular spectroscopy spectra as cassipourol, ß-sitosterol and α-amyrin. Globally, cassipourol and ß-sitosterol inhibit quorum sensing-regulated and -regulatory genes expression in las and rhl systems without affecting the global regulators gacA and vfr, whereas α-amyrin had no effect on the expression of these genes. These terpenoids disrupt the formation of biofilms at concentrations down to 12.5, 50 and 50 µM for cassipourol, ß-sitosterol and α-amyrin, respectively. Moreover, these terpenoids reduce the production of total exopolysaccharides and promote flagella-dependent motilities (swimming and swarming). The isolated terpenoids exert a wide range of inhibition processes, suggesting a complex mechanism of action targeting P. aeruginosa virulence mechanisms which support the wide anti-infectious use of this plant species in traditional Burundian medicine.

The Role of ß-Carboline Alkaloids in the Pathogenesis of Essential Tremor.

Essential tremor (ET) is one of the most prevalent neurological disorders in the world. Environmental factors have been implicated in the pathogenesis of ET. In particular, epidemiological studies have suggested that neurotoxic agents, especially ß-carboline alkaloids (ßCAs), might be generated through Maillard-type reaction. ßCAs are molecules which are members of a large group of heterocyclic amines (HCAs, the so-called products of cooking meat). ßCAs are highly tremorogenic in animals, producing a marked generalized action tremor soon after systemic administration in a wide range of laboratory animals such as mice, rats and monkeys. Administration of ßCAs remains currently the main experimental model of ET. We review the pathogenesis of ET, with a focus on the biochemistry of ßCAs, their occurrence and biological activity, their endogenous biosynthesis, their formation in food, their toxicokinetics and their neurotoxicity. We highlight open questions regarding the effects of ßCAs in humans.

Effect of lipid extracts of Nigella sativa L. seeds on the liver ATP reduction and alpha-glucosidase inhibition.

Various extracts from the seeds of Nigella sativa have been used in traditional folk medicine to treat inflammation, liver disorders and arthritis. These seeds have been experimentally shown to possess antioxidant and hepatoprotective properties. Beside the hypoglycaemic and hypolipidemic effects, this study was carried out to evaluate, in vitro, toxicological effect of lipid extracts from the Nigella sativa seeds. The tested fractions were: (i) defatted methanolic extract, (ii) total lipid extract obtained by hexane extraction from methanolic extract and (iii) neutral and polar lipid fractions. The fractions were assessed, in vitro, for their inhibitory activity potential on the enzyme alpha-glucosidase as suppressing the enzyme activity is one among the therapeutic approaches to attenuate postprandial hyperglycemia. High inhibition of alpha-glucosidase by the two polar lipid fractions (F6 and F7) was reflected by their IC50 (0.51±0.04mg/ml and 0.55±0.09mg/ml, respectively), compared to acarbose (0.53±0.06mg/ml) and thymoquinone (0.65±0.05mg/ml). The hypoglycaemic effect of the polar lipid fraction of Nigella sativa could be explained by the inhibition of alpha-glucosidase, which is one of early steps of carbohydrate metabolism. Toxicological evaluation was investigated on precision-cut rat liver slices (PCLS). On PCLS, lipid extracts reduced ATP levels by 27 to 35%. Results indicate suggest that Nigella sativa extracts don't show a hepatoprotective effect against acetaminophen, but don't exhibit a major hepatotoxicity when tested alone.

Organocatalysis paradigm revisited: are metal-free catalysts really harmless?

Catalysts are commonly used in polymer synthesis. Traditionally, catalysts used to be metallic compounds but some studies have pointed out their toxicity for human health and environment, and the removal of metal impurities from synthetic polymer is quite expensive. Organocatalysts have been intensively synthesized and are now widely used in ring-opening polymerization (ROP) reactions to address these issues. However, for most of them, there is not any evidence of their safety. The present study attempts to assess whether well-established organo-based ROP catalysts used for the preparation of FDA-approved polyesters may present a certain level of cytotoxicity. In vitro toxicity is evaluated using a methyl-thiazol-tetrazolium cytotoxicity assay on two cell models (FHs74Int and HepaRG). Among the investigated organocatalysts, only functionalized thiourea shows an important cytotoxicity on both cell models. 4-Dimethylaminopyridine (DMAP), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and meta-(trimethylammonio)phenolate betaine (m-BE) show cytotoxicity against HepaRG cell line only at a high concentration.

In vitro effects of Panax ginseng in aristolochic acid-mediated renal tubulotoxicity: apoptosis versus regeneration.

This in vitro study aimed to determine the effects of a Panax ginseng extract on aristolochic acid-mediated toxicity in HK-2 cells. A methanolic extract of ginseng (50 µg/mL) was able to reduce cell survival after treatment with 50 µM aristolochic acid for 24, 48, and 72 h, as evidenced by a resazurin reduction assay. This result was confirmed by a flow cytometric evaluation of apoptosis using annexin V-PI staining, and indicated higher apoptosis rates in cells treated with aristolochic acid and P. ginseng extract compared with aristolochic acid alone. However, P. ginseng extract by itself (5 and 50 µg/mL) increased the Ki-67 index, indicating an enhancement in cellular proliferation. Cell cycle analysis excluded a P. ginseng extract-mediated induction of G2/M cell cycle arrest such as the one typically observed with aristolochic acid. Finally, ß-catenin acquisition was found to be accelerated when cells were treated with both doses of ginseng, suggesting that the epithelial phenotype of renal proximal tubular epithelial cells was maintained. Also, ginseng treatment (5 and 50 µg/mL) reduced the oxidative stress activity induced by aristolochic acid after 24 and 48 h. These results indicate that the ginseng extract has a protective activity towards the generation of cytotoxic reactive oxygen species induced by aristolochic acid. However, the ginseng-mediated alleviation of oxidative stress did not correlate with a decrease but rather with an increase in aristolochic acid-induced apoptosis and death. This deleterious herb-herb interaction could worsen aristolochic acid tubulotoxicity and reinforce the severity and duration of the injury. Nevertheless, increased cellular proliferation and migration, along with the improvement in the epithelial phenotype maintenance, indicate that ginseng could be useful for improving tubular regeneration and the recovery following drug-induced kidney injury. Such dual activities of ginseng certainly warrant further in vivo studies.

Potential nephroprotective effects of the Chinese herb Angelica sinensis against cisplatin tubulotoxicity.

CONTEXT: Acute kidney injury (AKI) is often encountered in patients receiving cisplatin (CisPt), a chemotherapeutic drug that induces numerous toxic side effects. Techniques used to limit nephrotoxicity during CisPt treatment are not fully effective; about a third of patients experience AKI. New nephroprotective strategies, including pharmacological approaches, must be developed. OBJECTIVE: The present study investigated the nephroprotective potential of Angelica sinensis (Oliv.) Diels (Apiaceae) root towards CisPt tubulotoxicity. MATERIALS AND METHODS: HK-2 cells were incubated with CisPt (10 µM) and/or with a methanolic extract of A. sinensis (AS). Nephroprotective capacity was evaluated by means of cellular viability (resazurin assay) and apoptosis (annexin-V/PI staining), oxidative stress generation (H2DCF-DA oxidation), Ki-67 index (immunofluorescence), cell cycle analysis (DNA staining), cell migration rate (scratch assay), extracellular matrix deposition (collagen determination), and ß-catenin relocalization. RESULTS: CisPt decreased cell viability [76% versus Ctrl], which was associated with an increased apoptosis. Simultaneous treatment with 50 µg/ml AS enhanced cell survival [84% versus Ctrl] and decreased the apoptosis rate. AS could not alleviate CisPt-induced oxidative stress; but doses of 5 and 50 µg/ml raised the Ki-67 index [135 and 244% versus Ctrl] and cell migration rates [1.2 and 1.3-fold versus Ctrl]. Finally, both doses of AS limited the amount of collagen deposition [121.6 and 119.6% for 5 and 50 µg/ml, respectively, versus 131.0% for CisPt-treated cells] and prevented the relocalization of ß-catenin from the membrane to the nucleus. CONCLUSION: These results confirm the nephroprotective potential of A. sinensis and require further investigations aiming at identifying its active compounds.