Utilization of gallic acid to inhibit some toxic activities caused by Bothrops jararaca or B. jararacussu snake venoms.

Snake bite envenoming is a serious public health issue, affecting thousands of people worldwide every year, especially in rural communities of tropical and subtropical countries. Injection of venom into victims may cause hemorrhaging, blood coagulation imbalance, inflammation, pain, edema, muscle necrosis, and eventually, death. The official validated treatment recommended by governments is the administration of antivenom that efficiently prevents morbidity and mortality. However, this therapy does not effectively neutralize the local effects of Viperidae venoms which constitute one of the leading causes of disability or amputation of the affected limb. Thus, bioprospecting studies seeking for alternative therapies to complement antivenom should be encouraged, especially those investigating the blockage of local venomic toxicity. Plants produce a great diversity of metabolites with a wide range of pharmacological and biological properties. Therefore, the objective of this study was to assess the utilization of gallic acid, which is widely found in plants, against some toxic in vitro (coagulation, proteolytic, and hemolytic) or in vivo (edematogenic, hemorrhagic, and lethal) activities of Bothrops jararaca or B. jararacussu venom. Gallic acid was incubated with B. jararaca or B. jararacussu venom (incubation protocol), after which, in vitro or in vivo assays were performed. Additionally, a gel containing gallic acid was developed and topically applied over the skin of mice after injection of B. jararaca or B. jararacussu venom (treatment protocol), and then, a hemorrhagic assay was carried out. As a result, gallic acid inhibited the toxic activities, with variable efficacy, and the gallic acid gel neutralized B. jararaca or B. jararacussu venom-induced hemorrhagic activity. Gallic acid was devoid of in vitro toxicity as shown through a hemocompatibility test. Thus, these findings demonstrate the potential of gallic acid in the development of an alternative agent to treat victims of snake bites inflicted by Bothrops species.

Short-term exposure to the simple polyphenolic compound gallic acid induces neuronal hyperactivity in zebrafish larvae.

A growing body of evidence suggests that the biological effects of polyphenols are not restricted to antioxidant activity, but they exert a wide range of modulatory effects on metabolic pathways, cellular signaling and gene expression. In this study, we tested the minimum safe concentration of gallic acid (GA) in 72 hpf zebrafish larvae in order to evaluate the effects on the central nervous system and the behavioral response. We showed that a short exposure (30 min) induces the depletion of the two main excitatory and inhibitory neurotransmitters, Glu and GABA, respectively, in the larval nervous system. The acute impairment of GABAergic-glutamatergic balance was paralleled by an increase of the fosab neuronal activity marker in specific brain areas, such as the forebrain, olfactory bulbs, pallial area, ventral midbrain, tegmentum, and the medulla oblongata ventral area. The neuronal excitation was mirrored by the increased cumulative motor response. The inhibition of the olfactory epithelium with brief cadmium exposition suggests a direct involvement of olfaction in the larvae response to GA. Our results demonstrate that a brief exposure to GA induces motoneuronal hyperexcitability in zebrafish. The behavioral response was probably elicited through the activation of an odorous, or chemical, stimulus. The specificity of the activated neuronal territories suggests the involvement of additional signaling pathways. Although the underlying molecular mechanisms remain to be elucidated, our data support the hypothesis that GA acts as an excitatory molecule, capable of inducing a specific nerve response. These results offer a new vision on potential effects of GA.

Toxicological implications of amplifying the antibacterial activity of gallic acid by immobilisation on silica particles: A study on C. elegans.

Immobilisation of natural compounds on solid supports to amplify antimicrobial properties has reported successful results, but modifications to physico-chemical properties can also imply modifications from a toxicological viewpoint. This work aimed to study the immobilising process of gallic acid in the antibacterial activity of L. innocua and its toxicological properties in vivo using Caenorhabditis elegans. The experiment was based on obtaining the minimum bactericidal concentration for free and immobilised gallic acid by comparing lethality, locomotion behaviour, chemotaxis and thermal stress resistance on C.elegans at those concentrations. The results showed a lowering minimum bactericidal concentration and modifications to nematode responses. Increased lethality and velocity of movements was observed. Immobilisation increased the repellent effect of gallic acid with a negative chemotaxis index. Thermal stress resistance was also affected, with higher mortality for immobilised gallic acid compared to bare particles and free gallic acid. Thus despite evidencing a generalised increase in the toxicity of gallic acid in vivo, lowering the minimum bactericidal concentration allowed a bacterial reduction of 99 % with less than one third of mortality for the nematodes exposed to free gallic acid.

Are Supplements Safe? Effects of Gallic and Ferulic Acids on In Vitro Cell Models.

Polyphenols display health-promoting properties linked to their biological activities. They are initially absorbed in the small intestine, then they are largely metabolized in the colon, whereupon they are able to exert systemic effects. The health-promoting properties of polyphenols have led to the development of food supplements, which are also largely consumed by healthy people, even if data on their safety are still yet lacking. In the present paper, the content of gallic acid and ferulic acid was analyzed in two supplements, and shown to be higher than the relative contents found in fruit and flour. To evaluate the effects of these phenolic compounds on epithelial intestinal tissue, gallic and ferulic acids were added to a new in vitro model of the intestinal wall at different concentrations. The effects on viability, proliferation and migration of these compounds were respectively tested on three different cell lines (Caco2, L929 and U937), as well as on a tridimensional intestinal model, composed of a mucosal layer and a submucosa with fibroblasts and monocytes. Results indicated that gallic and ferulic acids can exert toxic effects on in vitro cell models at high concentrations, suggesting that an excessive and uncontrolled consumption of polyphenols may induce negative effects on the intestinal wall.

Toxicity and Selective Biochemical Assessment of Quercetin, Gallic Acid, and Curcumin in Zebrafish.

In recent years, numerous research outcomes were established on various naturally occurring compounds that have been shown to have beneficial antioxidant and other biological activities. Antioxidant defence mechanism plays a vital role in combating various diseases mainly due to oxidative stress. However, various models have been utilized to identify their bioactivities using these compounds (quercetin, gallic acid and curcumin). Their toxicity level also has to be explored to determine the threshold levels on the usage of these compounds. In this study, we investigated the lethal concentration of these compounds and abnormalities, biochemical and morphological changes in zebrafish embryo (Danio rerio). Toxicity level was evaluated by calculating the LD50 on the embryonic stages at 24, 48 and 72 h. Antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and biological assays such as lipid peroxidation, protein estimation were performed. Microscopic evaluations were also observed to find out morphological abnormalities. However, these naturally derived compounds are reported to have their protective and curative role in many health complications. From the above assays, we are studying the effect of the drugs in both biochemical and molecular way in the zebrafish model organism.

Acute and 28-days repeated dose sub-acute toxicity study of gallic acid in albino mice.

Gallic acid is a phenolic acid ubiquitously present in numerous medicinal plants and food beverages. Gallic acid is also a potent anti-oxidant phytochemical possessing numerous medicinal potentials against various ailments such as diabetes, hypercholesterolemia and other life-threatening diseases including malignancy. Present study was aimed to evaluate acute and sub-acute toxicity of gallic acid in albino mice. The primary aim of the study was to investigate gallic acid prompted PPAR-α/γ activation associated adverse events. Acute toxicity of gallic acid was determined in albino mice and 28-days sub-acute toxicity study was carried out in male and female albino mice at three dose levels, 100, 300 and 900 mg/kg/day, p.o. LD50 of gallic acid was found to be greater than 2000 mg/kg in mice. Hematological investigation did not show any alteration in transaminases and other blood homeostasis parameters. Gross necropsy showed non-significant alteration upon gallic acid administration. Histopathological finding suggested no significant alteration in tissue histology with slight fatty cells in bone marrow indicating non-significant bone marrow suppression, also no obvious effect was observed on hematological parameters. High dose of gallic acid (900 mg/kg/day) for 28 days did not produce any significant alteration in morphological and behavioral parameters. Histopathological finding also supports safety of gallic acid in mice.

Toxicity of phenolic compounds to entomopathogenic nematodes: A case study with Heterorhabditis bacteriophora exposed to lentisk (Pistacia lentiscus) extracts and their chemical components.

Insects show adaptive plasticity by ingesting plant secondary compounds, such as phenolic compounds, that are noxious to parasites. This work examined whether exposure to phenolic compounds affects the development of insect parasitic nematodes. As a model system for parasitic life cycle, we used Heterorhabditis bacteriophora (Rhabditida; Heterorhabditiade) grown with Photorhabdita luminescens supplemented with different concentrations of plant phenolic extracts (0, 600, 1200, 2400 ppm): a crude ethanol extract of lentisk (Pistacia lentiscus) or lentisk extract fractionated along a scale of hydrophobicity with hexane, chloroform and ethyl acetate; and flavonoids (myricetin, catechin), flavanol-glycoside (rutin) or phenolic acids (chlorogenic and gallic acids). Resilience of the nematode to phenolic compounds was stage-dependent, with younger growth stages exhibiting less resilience than older growth stages (i.e., eggs < young juveniles < young hermaphrodites < infective juveniles < mature hermaphrodites). At high concentrations, all of the phenolic compounds studied were lethal to eggs and young juveniles. The nematodes were able to survive in the presence of medium and low concentrations of all studied compounds, but very few of those treatments allowed for reproduction beyond the infective juvenile stage and, at low concentrations, the crude 70% ethanol extract, chloroform and hexane extracts, and myricetin were associated with some impaired reproduction. The ethyl-acetate fraction and gallic acid were extremely lethal to the young stages and allowed almost no development beyond the infective juvenile stage. We conclude that exposure of infective juveniles to phenolics before they infect insects and post-infection exposure of other nematode developmental stages may affect the initiation of the infection, suggesting that the chemistry of dietary phenolics may limit H. bacteriophora's infection of insects.

The toxic effect of gallic acid on biochemical factors, viability and proliferation of rat bone marrow mesenchymal stem cells was compensated by boric acid.

OBJECTIVE: Gallic acid (GA) and boron are found in many plants. Our previous studies showed 6 ng/ml boric acid (BA) had positive effect on biochemistry of rat bone marrow mesenchymal stem cells (MSCs) and their osteogenic differentiation. Therefore, we investigate the effect of different doses of GA alone and in the presence of BA on MSCs. MATERIALS AND METHODS: the viability of MSCs was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue at 12, 24 and 36 h in presence of different concentration of GA. Then 30 and 120 µM of GA as well as 6 ng/ml of BA in 36 h were selected for further study. The proliferation, Morphology, sodium and potassium level, concentration of calcium, activity of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as well as malondialdehyde (MDA) concentration, total antioxidant capacity (FRAP) and activity of superoxide dismutase (SOD) and catalase (CAT) were estimated. RESULT: Results showed GA alone reduced viability, proliferation, nuclear diameter and cytoplasm area. In addition, GA showed anaerobic metabolic shift but no change in MDA and scavenging enzymes. Both concentration of GA caused elevation of FRAP, whereas only at 120 µM increased the sodium-potassium and reduced calcium. The co-treatment of GA and BA improves the viability, proliferation and morphology of the cells. In addition, co-treatment compensated the metabolic shift caused by GA and could balance the potassium level and FRAP as it was raised by GA. CONCLUSION: Although GA content of tea is harmful to the cells but simultaneous consumption of fruits and vegetables as a rich source of boron might compensate the damaging effect of GA.

Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor.

The recent 2014-2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.

Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio).

Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi-static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 ßestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017.

Layered Double Hydroxide as a Vehicle to Increase Toxicity of Gallate Ions against Adenocarcinoma Cells.

The antineoplasic activity of gallic acid has been reported. This compound induces apoptosis and inhibits the growth of several neoplasic cells. However, this molecule is easily oxidized and degraded in the body. The aim of this work was to intercalate gallate ions into layered double hydroxide (LDH) nanoparticles under controlled conditions to reduce oxidation of gallate and to evaluate its toxicity against the A549 adenocarcinoma cell line. An isopropanol medium under nitrogen atmosphere was adequate to intercalate gallate ions with a lesser oxidation degree as detected by electron spin resonance spectroscopy. Concentrations of the hybrid LDH-gallate nanoparticles between 0.39 and 25 µg/mL reduced the cell viability to 67%, while the value reached with the pure gallic acid and LDH was 90% and 78%, respectively, thus proving that the combination of gallate ions with the inorganic nanoparticles increases the toxicity potential within this dose range.

Pentyl Gallate Nanoemulsions as Potential Topical Treatment of Herpes Labialis.

Previous studies have demonstrated the antiherpes activity of pentyl gallate (PG), suggesting that it could be a promising candidate for the topical treatment of human herpes labialis. PG low aqueous solubility represents a major drawback to its incorporation in topical dosage forms. Hence, the feasibility of incorporating PG into nanoemulsions, the ability to penetrate the skin, to inhibit herpes simplex virus (HSV)-1 replication, and to cause dermal sensitization or toxicity were evaluated. Oil/water nanoemulsions containing 0.5% PG were prepared by spontaneous emulsification. The in vitro PG distribution into porcine ear skin after topical application of nanoemulsions was assessed, and the in vitro antiviral activity against HSV-1 replication was evaluated. Acute dermal toxicity and risk of dermal sensitization were evaluated in rat model. Nanoemulsions presented nanometric particle size (from 124.8 to 143.7 nm), high zeta potential (from -50.1 to -66.1 mV), loading efficiency above 99%, and adequate stability during 12 months. All formulations presented anti-HSV-1 activity. PG was able to reach deeper into the dermis more efficiently from the nanoemulsion F4. This formulation as well as PG were considered safe for topical use. Nanoemulsions seem to be a safe and effective approach for topically delivering PG in the treatment of human herpes labialis infection.

Allelopathic potential and ecotoxicity evaluation of gallic and nonanoic acids to prevent cyanobacterial growth in lentic systems: A preliminary mesocosm study.

The increase in anthropogenic nutrient loading affecting many freshwater ecosystems combined with global warming may lead to cyanobacterial blooms on an increasingly frequent basis. Among the various physicochemical and biological methods which have been proposed to rapidly control blue-green algae growth, the use of plant-derived substances such as allelochemicals has gained great interest as an environment-friendly approach. The primary aim of this work was to evaluate the efficiency of gallic and nonanoic acid application to preemptively inhibit cyanobacterial growth in lentic hydrosystems. In order to address the process feasibility under realistic exposure scenarios, thirteen outdoor freshwater mesocosms (unit volume: 3m(3)) were designed, each containing phytoplankton (including local blue-green algae species) and various non-target organisms from higher trophic levels (Physa, Lymnaea, Gammarus, and Scardinius erythrophthalmus). After an 8-week mesocosm stabilization period, a full factorial design based on the presence/absence of gallic acid (GA) and nonanoic acid (NA) (including a control group) was implemented into the exposure tanks. Regular monitoring of major phytoplankton taxa was conducted during a 28-day experiment using an on-line fluorometer. The main results suggested that gallic acid was more efficient than nonanoic acid at limiting cyanobacterial growth at concentrations as low as 1 mg L(-1). Successive gallic acid applications (at 1, 2 and 4 mg L(-1)) at the early stages of cyanobacterial growth did not allow the complete elimination of blue-green algae from the mesocosms. However, the specificity of the allelopathic effect of gallic acid towards cyanobacteria was compatible with the maintenance of a primary productivity in the treated tanks as indicated by the photoautotrophic growth of other algal taxa. Finally, no biomarker induction signal could be reported in non-target species. Further gallic acid application trials in lentic systems such as small freshwater ponds may help to design innovative allelopathy-based aquatic ecotechnologies.

Antiviral activity of theaflavin digallate against herpes simplex virus type 1.

Tea is the second most consumed drink in the world. The beneficial effects of tea have been mostly attributed to its catechin content. Black tea is derived from the leaves of Camellia sinensis plant, and it is rich in theaflavin polyphenols, in particular theaflavin (TF1), theaflavin-3-monogallate (TF2A), theaflavin-3'-monogallate (TF2B), and theaflavin-3,3'-digallate (TF3). Vero and A549 cells were used to evaluate the effect of purified individual black tea theaflavins as anti-herpes simplex virus 1 agents. With the rise of HSV resistant strains, there is a critical need to develop novel antiherpesviral treatments. Results of the cytotoxicity assay tested by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] showed that TF1, TF2, and TF3 are not toxic to Vero and A549 cells at a concentration up to 75 µM. The antiviral activity of the individual theaflavins was tested by plaque reduction assay, MTS assay, flow cytometric analysis and confocal microscopy observations. The results showed that TF1, TF2, and TF3 exhibit potent, dose-dependent anti-HSV-1 effect, with TF3 being the most efficient in both Vero and A549 cells. A concentration of 50 µM TF3 and above was sufficient to inhibit >99% of the production of HSV-1 viral particles. The anti-HSV-1 effect of TF3 is due to a direct effect on the virions, and treating Vero or A549 cells with TF3 for 1h prior to infection, or treating the cells at different times post infection does not inhibit HSV-1 production. TF3 is stable at vaginal pH, indicating its potential to be a promising natural and affordable remedy against herpes simplex viral infections.

Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio.

Gallic and pelargonic acids are naturally found in a variety of plants and food products. Despite their extensive use in man-made applications, little is known regarding their potential risks to aquatic vertebrates. The aim of this work was to assess the acute toxicity of these polyphenolic and fatty acid compounds to the zebrafish. In order to get insights into sublethal effects, the enzyme activity of usual biomarkers related to oxidative stress and biotransformation were also assessed in fish. These latter included total superoxide dismutase, catalase as well as total glutathione peroxidase for antioxidant defence mechanisms and glutathione S-transferase for biotransformation related enzyme. Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100 mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L). Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose-dependent induction of glutathione peroxidase and glutathione S-transferase was reported following gallic acid exposure at the tested concentrations of 10, 20 and 40 mg/L, with the exception of 100 mg/L of substance where basal activity levels were reported. In the case of pelargonic acid, there was no change in antioxidant enzyme activity while an inhibition of glutathione S-transferase was observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The results concerning sublethal effects on biological parameters of zebrafish highlighted thereby the need for further investigations following chronic exposure to both organic acids.

Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging.

In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr(3+) near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr(3+) nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (~15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging.

In vitro protection of biological macromolecules against oxidative stress and in vivo toxicity evaluation of Acacia nilotica (L.) and ethyl gallate in rats.

BACKGROUND: Recently, enormous research has been focused on natural bioactive compounds possessing potential antioxidant and anticancer properties using cell lines and animal models. Acacia nilotica (L.) is widely distributed in Asia, Africa, Australia and Kenya. The plant is traditionally used to treat mouth, ear and bone cancer. However, reports on Acacia nilotica (L.) Wild. Ex. Delile subsp. indica (Benth.) Brenan regarding its toxicity profile is limited. Hence in this study, we investigated the antioxidant capacity and acute toxicity of ethyl gallate, a phenolic antioxidant present in the A. nilotica (L.) leaf extract. METHODS: The antioxidant activity of ethyl gallate against Fenton's system (Fe3+/H2O2/ascorbic acid) generated oxidative damage to pBR322 DNA and BSA was investigated. We also studied the interaction of ethyl gallate to CT-DNA by wave scan and FTIR analysis. The amount of ethyl gallate present in the A. nilotica (L.) leaf extract was calculated using HPLC and represented in gram equivalence of ethyl gallate. The acute toxicity profile of ethyl gallate in the A. nilotica (L.) leaf extract was analyzed in albino Wistar rats. Measurement of liver and kidney function markers, total proteins and glucose were determined in the serum. Statistical analysis was done using statistical package for social sciences (SPSS) tool version 16.0. RESULTS: Ethyl gallate was found to be effective at 100 µg/mL concentration by inhibiting the free radical mediated damage to BSA and pBR322 DNA. We also found that the interaction of ethyl gallate and A. nilotica (L.) leaf extract to CT-DNA occurs through intercalation. One gram of A. nilotica (L.) leaf extract was found to be equivalent to 20 mg of ethyl gallate through HPLC analysis. Based on the acute toxicity results, A. nilotica (L.) leaf extract and ethyl gallate as well was found to be non-toxic and safe. CONCLUSIONS: Results revealed no mortality or abnormal biochemical changes in vivo and the protective effect of A. nilotica (L.) leaf extract and ethyl gallate on DNA and protein against oxidative stress in vitro. Hence, A. nilotica (L.) leaf extract or ethyl gallate could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

Modulation of human miR-17-3p expression by methyl 3-O-methyl gallate as explanation of its in vivo protective activities.

SCOPE: Methyl-3-O-methyl gallate (M3OMG) possesses in vivo antioxidant activity due to the partial restoration of the antioxidant enzymes, whose expression is altered in oxidative stress. Literature data suggest that miR-17-3p is a microRNA involved in the regulation of cellular redox status, interfering with transcription of the mRNAs responsible for the synthesis of antioxidant enzymes. To obtain deeper insight into the potential mechanism of action of M3OMG, the aim of this study was to investigate its effect on the expression levels of miR-17-3p in human cells. METHODS AND RESULTS: Peripheral blood mononuclear cells and EVC-304 cells were treated with increasing subtoxic concentrations of M3OMG. The expression levels of miR-17-3p, extracted from cells and exosomes, were determined by quantitative real-time PCR. M3OMG induced a decrease in the miR-17-3p levels, and an increase in the levels of mRNA coding for the antioxidant enzymes, when compared to the control samples. Differently, in exosomes the expression levels of miR-17-3p were depended on the compound, its concentration, and the type of cell. CONCLUSION: These results suggest a potential mechanism of action of M3OMG that, inducing the reduction of the levels of miR-17-3p and the increase of mRNA coding for antioxidant enzymes, allows to these latter to perform their protective effects.

In vitro sustained release study of gallic acid coated with magnetite-PEG and magnetite-PVA for drug delivery system.

The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.