Ascorbic acid potentiates photodynamic inactivation mediated by octyl gallate and blue light for rapid eradication of planktonic bacteria and biofilms.

This study reported for the first time that Ascorbic acid (AA) could appreciably boost the efficiency of Octyl gallate (OG)-mediated photodynamic inactivation (PDI) on Escherichia coli and Staphylococcus aureus in planktonic and biofilm states. The combination of OG (0.075 mM) and AA (200 mM) with 420 nm blue light (212 mW/cm2) led to a >6 Log killing within only 5 min for E. coli and S. aureus and rapid eradication of biofilms. The mechanism of action appears to be the generation of highly toxic hydroxyl radicals (•OH) via photochemical pathways. OG was exposed to BL irradiation to generate various reactive oxygen radicals (ROS) and the addition of AA could transform singlet oxygen (1O2) into hydrogen peroxide (H2O2), which could further react with AA to generate enormous •OH. These ROS jeopardized bacteria and biofilms by nonspecifically attacking various biomacromolecules. Overall, this PDI strategy provides a powerful microbiological decontamination modality to guarantee safe food products.

Inhibitory effects and reactions of gallic acid, catechin, and procyanidin B2 with nitrosation under stomach simulating conditions.

Nitrite widely exists in meat products, and has the functions of bacteriostasis, antisepsis, and color development. However, in an acidic environment, nitrite will react with amines, and further generate nitrosamines with carcinogenic and teratogenic effects. Polyphenols have good antioxidant and nitrite-scavenging effects. This study aimed to evaluate the inhibitory effects of gallic acid, catechin, and procyanidin B2 on the nitrosation reaction under stomach simulating conditions and discuss the potential inhibitory mechanism. The nitrite scavenging rate and nitrosamine synthesis blocking rate of gallic acid, catechin, and procyanidin B2 under different reaction times and contents was determined by UV-vis spectrophotometry. The possible products of the reaction of the three polyphenols with nitrite were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) to reveal the mechanism of inhibiting nitrification. The results showed that the scavenging rate of the three polyphenols on nitrite and the blocking rate of nitrosamine synthesis increased with the increase of the content and reaction time. The ability of the three polyphenols to inhibit nitrosation was catechin > procyanidin B2 > gallic acid. HPLC-MS analysis showed that under simulated gastric juice conditions, the three phenolics were oxidized by nitrous acid to form their semiquinone radicals as the intermediates and nitrosated derivatives, while nitrite might be converted to ˙NO. These results suggested that gallic acid, catechin, and procyanidin B2 could inhibit nitrosation reactions in an acidic environment and may be used as food additives to reduce nitrite residues and nitrosamines in food.

Toward Enhanced Antioxidant and Protective Potential: Conjugation of Corn Cob Xylan with Gallic Acid as a Novel Approach.

Maize ranks as the second most widely produced crop globally, yielding approximately 1.2 billion tons, with corn cob being its primary byproduct, constituting 18 kg per 100 kg of corn. Agricultural corn production generates bioactive polysaccharide-rich byproducts, including xylan (Xyl). In this study, we used the redox method to modify corn cob xylan with gallic acid, aiming to enhance its antioxidant and protective capacity against oxidative stress. The conjugation process resulted in a new molecule termed conjugated xylan-gallic acid (Xyl-GA), exhibiting notable improvements in various antioxidant parameters, including total antioxidant capacity (1.4-fold increase), reducing power (1.2-fold increase), hydroxyl radical scavenging (1.6-fold increase), and cupric chelation (27.5-fold increase) when compared with unmodified Xyl. At a concentration of 1 mg/mL, Xyl-GA demonstrated no cytotoxicity, significantly increased fibroblast cell viability (approximately 80%), and effectively mitigated intracellular ROS levels (reduced by 100%) following oxidative damage induced by H2O2. Furthermore, Xyl-GA exhibited non-toxicity toward zebrafish embryos, offered protection against H2O2-induced stress, and reduced the rate of cells undergoing apoptosis resulting from H2O2 exposure. In conclusion, our findings suggest that Xyl-GA possesses potential therapeutic value in addressing oxidative stress-related disturbances. Further investigations are warranted to elucidate the molecular structure of this novel compound and establish correlations with its pharmacological activities.

Gallic Acid-Based Hydrogels for Phloretin Intestinal Release: A Promising Strategy to Reduce Oxidative Stress in Chronic Diabetes.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by abnormalities in insulin secretion and/or action. In patients with diabetes, complications such as blindness, delayed wound healing, erectile dysfunction, renal failure, heart disease, etc., are generally related to an increase in ROS levels which, when activated, trigger hyperglycemia-induced lesions, inflammation and insulin resistance. In fact, extensive cell damage and death occurs mainly due to the effect that ROS exerts at the level of cellular constituents, causing the deterioration of DNA and peroxidation of proteins and lipids. Furthermore, elevated levels of reactive oxygen species (ROS) and an imbalance of redox levels in diabetic patients produce insulin resistance. These destructive effects can be controlled by the defense network of antioxidants of natural origin such as phloretin and gallic acid. For this reason, the objective of this work was to create a nanocarrier (hydrogel) based on gallic acid containing phloretin to increase the antioxidant effect of the two substances which function as fundamental for reducing the mechanisms linked to oxidative stress in patients suffering from chronic diabetes. Furthermore, since the bioavailability problems of phloretin at the intestinal level are known, this carrier could facilitate its release and absorption. The obtained hydrogel was characterized using Fourier transform infrared spectroscopy (FT-IR). Its degree of swelling (a%) and phloretin release were tested under pH conditions simulating the gastric and intestinal environment (1.2, 6.8 and 7.4). The antioxidant activity, inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a free radical source, was evaluated for four hours. All results showed that gallate hydrogel could be applied for releasing intestinal phloretin and reducing the ROS levels.

Neuroprotective Effects of Polysaccharides and Gallic Acid from Amauroderma rugosum against 6-OHDA-Induced Toxicity in SH-SY5Y Cells.

The pharmacological activity and medicinal significance of Amauroderma rugosum (AR) have rarely been documented. We examined the antioxidant and neuroprotective effects of AR on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in an SH-SY5Y human neuroblastoma cell model of Parkinson's disease (PD) and explored the active ingredients responsible for these effects. The results showed that the AR aqueous extract could scavenge reactive oxygen species and reduce SH-SY5Y cell death induced by 6-OHDA. In addition, the AR aqueous extract increased the survival of Caenorhabditis elegans upon juglone-induced toxicity. Among the constituents of AR, only polysaccharides and gallic acid exhibited antioxidant and neuroprotective effects. The AR aqueous extract reduced apoptosis and increased the expression of phospho-Akt, phospho-mTOR, phospho-MEK, phospho-ERK, and superoxide dismutase-1 in 6-OHDA-treated SH-SY5Y cells. The polysaccharide-rich AR extract was slightly more potent than the aqueous AR extract; however, it did not affect the expression of phospho-Akt or phospho-mTOR. In conclusion, the AR aqueous extract possessed antioxidant and neuroprotective properties against 6-OHDA-induced toxicity in SH-SY5Y cells. The mechanism of action involves the upregulation of the Akt/mTOR and MEK/ERK-dependent pathways. These findings indicate the potential utility of AR and its active ingredients in preventing or treating neurodegenerative disorders associated with oxidative stress such as PD.

Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides.

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.

Investigation of the General Molecular Mechanisms of Gallic Acid via Analyses of Its Transcriptome Profile.

Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase ß and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses.

Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid.

PURPOSE: Oral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. MATERIALS AND METHODS: Gallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel. UV-visible (UV) spectrophotometry verified Zn-GANP synthesis. TEM, DLS, and FTIR were utilized to investigate ZnO-NPs' characteristics. Rats were orally exposed to DEN for 8 weeks at 20 mg/kg five times per week, followed by intraperitoneal injection of Zn-GANPs at 20 mg/kg for 5 weeks. Using oxidative stress, anti-inflammatory, liver function, histologic, apoptotic, and cell cycle parameters for evaluating Zn-GANPs treatment. RESULTS: DEN exposure elevated inflammatory markers (AFP and NF-κB p65), transaminases (AST, ALT), γ-GT, globulin, and total bilirubin, with reduced protein and albumin levels. It also increased MDA levels, oxidative liver cell damage, and Bcl-2, while decreasing caspase-3 and antioxidants like GSH, and CAT. Zn-GANPs significantly mitigated these effects and lowered lipid peroxidation, AST, ALT, and γ-GT levels, significantly increased CAT and GSH levels (p<0.05). Zn-GANPs caused S and G2/M cell cycle arrest and G0/G1 apoptosis. These results were associated with higher caspase-3 levels and lower Bcl-2 and TGF-ß1 levels. Zn-GANPs enhance and restore the histology and ultrastructure of the liver in DEN-induced rats. CONCLUSION: The data imply that Zn-GANPs may prevent and treat DEN-induced liver damage and carcinogenesis.

Synergistic Antibacterial Activity of Gallic Acid Based Chalcone Indl 2 by Inhibiting Efflux Pump Transporters.

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps.

Comments on "Cocrystallization of 5-fluorouracil with gallic acid: A novel 5-fluorouracil cocrystal displaying synergistic anti-tumor activity both in oral and intraperitoneal injection administration".

This commentary highlights the significance of the solution stability and preparation of a solution of cocrystal in evaluating anti-tumor activity. It introduces a challenging issue regarding improving the biological activity of an API in cocrystal form.

Antiproliferative and Antimigratory Activity of Poly-gallic Acid in Cancer Cell Lines.

BACKGROUND/AIM: Enzyme-mediated grafting of poly (gallic acid) (PGAL) and L-arginine and a-L-lysine onto PGAL produces reactive oxygen species (ROS)-suppressor multiradical molecules with low cytotoxicity, high thermostability and water solubility with cancer treatment potential. This study examined the anticancer effects of these molecules in hepatic (HepG2, ATCC HB-8065), breast (MCF7, ATCC HTB-22), and prostate (PC-3, ATCC CRL-1435 and DU 145, ATCC HTB-81) cancer cell lines, as well as in fibroblasts from healthy human skin as control cells. MATERIALS AND METHODS: PGAL was synthesized by the oxidative polymerization of the naturally abundant GA using laccase from Trametes versicolor. Insertions of amino acids L-arginine and α-L-lysine on the PGAL chain were carried out by microwave. The cells of dermal fibroblast (Fb) were obtained from primary skin cultures and isolated from skin biopsies. The cancer cells lines of hepatic (HepG2), breast (MCF7), and prostate (PC-3, DU 145) were obtained from ATCC. The viability of the cancer cells and the primary culture was obtained by the MTT assay. Proliferation was demonstrated by crystal violet assay. Cell migration was determined by Wound healing assay. Finally, cell cycle analysis was carried out with cells. RESULTS: The results show that 200 µg/ml of PGAL cultured in vitro with prostate cancer cells decreased viability, proliferation, and migration, as well as arrested cells in the G1 and S phases of the cell cycle. In contrast, the dermal fibroblasts and the hepatic line remained unaffected. The random grafting of L-Arg and a-L-Lys onto the PGAL chain also decreased the viability of prostate cancer cells. CONCLUSION: PGAL and PGAL-grafted amino acids are potential adjuvants for prostate cancer treatment, with improved physicochemical characteristics compared to GA.

Gallic acid: design of a pyrogallol-containing hydrogel and its biomedical applications.

Polyphenol hydrogels have garnered widespread attention due to their excellent adhesion, antioxidant, and antibacterial properties. Gallic acid (GA) is a typical derivative of pyrogallol that is used as a hydrogel crosslinker or bioactive additive and can be used to make multifunctional hydrogels with properties superior to those of widely studied catechol hydrogels. Furthermore, compared to polymeric tannic acid, gallic acid is more suitable for chemical modification, thus broadening its range of applications. This review focuses on multifunctional hydrogels containing GA, aiming to inspire researchers in future biomaterial design. We first revealed the interaction mechanisms between GA molecules and between GA and polymers, analyzed the characteristics GA imparts to hydrogels and compared GA hydrogels with hydrogels containing catechol. Subsequently, in this paper, various methods of integrating GA into hydrogels and the applications of GA in biomedicine are discussed, finally assessing the current limitations and future development potential of GA. In summary, GA, a natural small molecule polyphenol with excellent functionality and diverse interaction modes, has great potential in the field of biomedical hydrogels.

Magnesium Ion-Doped Mesoporous Bioactive Glasses Loaded with Gallic Acid Against Myocardial Ischemia/Reperfusion Injury by Affecting the Biological Functions of Multiple Cells.

Introduction: Excessive generation of reactive oxygen species (ROS) following myocardial ischemia-reperfusion (I/R) can result in additional death of myocardial cells. The rapid clearance of ROS after reperfusion injury and intervention during subsequent cardiac repair stages are crucial for the ultimate recovery of cardiac function. Methods: Magnesium-doped mesoporous bioactive glasses were prepared and loaded with the antioxidant drug gallic acid into MgNPs by sol-gel method. The antioxidant effects of MgNPs/GA were tested for their pro-angiogenic and anti-inflammatory effects based on the release characteristics of GA and Mg2+ from MgNPs/GA. Later, we confirmed in our in vivo tests through immunofluorescence staining of tissue sections at various time points that MgNPs/GA exhibited initial antioxidant effects and had both pro-angiogenic and anti-inflammatory effects during the cardiac repair phase. Finally, we evaluated the cardiac function in mice treated with MgNPs/GA. Results: We provide evidence that GA released by MgNPs/GA can effectively eliminate ROS in the early stage, decreasing myocardial cell apoptosis. During the subsequent cardiac repair phase, the gradual release of Mg2+ from MgNPs/GA stimulated angiogenesis and promoted M2 macrophage polarization, thereby reducing the release of inflammatory factors. Conclusion: MgNPs/GA acting on multiple cell types is an integrated solution for comprehensive attenuation of myocardial ischaemia-reperfusion injury and cardiac function protection.

Evaluation of the antiparasitic and antifibrotic effects of gallic acid on experimental hepatic schistosomiasis mansoni.

Schistosomiasis afflicts approximately 120 million individuals globally. The hepatic pathology that occurs due to egg-induced granuloma and fibrosis is commonly attributed to this condition. However, there is currently no efficacious treatment available for either of these conditions.Our study aimed to investigate the potential antifibrotic and antiparasitic properties of different doses of gallic acid (GA) in experimental schistosomiasis mansoni. In addition, we investigated the outcomes of co-administering it with the standard anti-schistosomiasis treatment, praziquantel (PZQ).In experiment I, Schistosoma mansoni-infected mice were administered GA at doses of 10, 20, or 40 mg/kg. Their effectiveness was evaluated through parasitological (worm and egg loads, granuloma number and diameter), pathological (fibrosis percentage and H-score of hepatic stellate cells (HSCs)), and functional (liver enzymes) tests. In experiment II, we investigated the optimal dosage that yielded the best outcomes. This dosage was administered in conjunction with PZQ and was evaluated regarding the parasitological, pathological, functional, and immunological (fibrosis-regulating cytokines) activities.Our findings indicate that the administration of 40 mg/kg GA exhibited the highest level of effectiveness in experiment I. In experiment II, it exhibited lower antiparasitic efficacy in comparison to PZQ. However, it surpassed PZQ in other tests. It showed enhanced outcomes when combined with PZQ.In conclusion, our findings reveal that GA only slightly increased the antischistosomal activity of PZQ. However, it was linked to decreased fibrosis, particularly when administrated with PZQ. Our pilot study identifies GA as a natural antifibrotic agent, which could be administered with PZQ to mitigate the development of fibrosis.

Gallic acid induces osteoblast differentiation and alleviates inflammatory response through GPR35/GSK3ß/ß-catenin signaling pathway in human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Gallic acid (GA) possesses various beneficial functions including antioxidant, anticancer, anti-inflammatory as well as inhibiting osteoclastogeneis. However, effects on osteogenic differentiation, especially in human ligament periodontal (hPDL) cells, remain unclear. Thus, the aim of this study was to evaluate the function of GA on osteogenesis and anti-inflammation in hPDL cells and to explore the involved underlying mechanism. METHODS: Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) treatment was used as a model for periodontitis. ROS production was determined by H2DCFDA staining. Trans-well and wound healing assays were performed for checking the migration effect of GA. Alizarin red and alkaline phosphatase activity (ALP) assays were performed to evaluate osteogenic differentiation. Osteogenesis and inflammatory-related genes and proteins were measured by real-time PCR and western blot. RESULTS: Our results showed that GA-treated hPDL cells had higher proliferation and migration effect. GA inhibited ROS production-induced by Pg-LPS. Besides, GA abolished Pg-LPS-induced inflammation cytokines (il-6, il-1ß) and inflammasome targets (Caspase-1, NLRP3). In addition, GA promoted ALP activity and mineralization in hPDL cells, lead to enhance osteoblast differentiation process. The effect of GA is related to G-protein-coupled receptor 35 (GPR35)/GSK3ß/ß-catenin signaling pathway. CONCLUSION: GA attenuated Pg-LPS-induced inflammatory responses and periodontitis in hPDL cells. Taken together, GA may be targeted for therapeutic interventions in periodontal diseases.

Ultrasonically functionalized chitosan-gallic acid films inactivate Staphylococcus aureus through envelope-disruption under UVA light exposure.

The significant threat of foodborne pathogens contamination has continuously promoted the development of efficient antimicrobial food packaging materials. Here, an antimicrobial film was prepared with gallic acid-grafted-chitosan (CS/GA) that obtained by a two-step ultrasound method. The resultant films exhibited good transparency, improved UV barrier performance, and enhanced mechanical strength. Specifically, with the grafting of 1.2 % GA, the UV blocking ability of CS/GA film at 400 nm was significantly increased by 19.7 % and the tensile strength was nearly two times higher than that of CS film. Moreover, the CS/GA films exhibited an inspiring photoactivated bactericidal ability under 400 nm UVA light irradiation that eradicated almost 99.9 % of Staphylococcus aureus (S. aureus) cells within 60 min. To gain more insights into the antibacterial mechanism, the treated S. aureus cells were further investigated by visualizing bacterial ultrastructure and analyzing membrane properties. The results pointed to the peptidoglycan layer as the primary action target when bacteria come into contact with CS/GA films. Afterward, the intracellular oxidative lesions, disrupted bacterial integrity, and disordered membrane functional properties collectively resulted in eventual cell death. The findings revealed the unique peptidoglycan targeting and membrane disruptive mechanisms of CS/GA films, confirming the application values in controlling foodborne pathogens.

Evaluation of the acute toxicity of ellagic acid and gallic acid incorporated in Poloxamer407® gel, in Zophobas morio larvae.

Gallic acid (GA) has antioxidant, anti-inflammatory and antimicrobial properties, while ellagic acid (EA) demonstrates anticancer, antiviral and photoprotective activity. In this study, the combination of these substances incorporated into a poloxamer gel was tested to verify the individual effect of the substances, in addition to taking advantage of a probable complementary effect, aiming to provide additional therapeutic benefits. As a result of the incorporation, formulations containing GA, EA and GA + EA were obtained, which were evaluated for the effects of the Freeze-thaw cycle on pH, which revealed a significant decrease (p < 0.05) in most samples, including the vehicle (without drug) and the gel containing both drugs. No sample showed variation outside the normal pH range for the skin, with values ranging from 4.8 to 6.0. Regarding conductivity, the GA, EA and GA + EA formulations showed a reduction (p < 0.05) after the freeze-thaw cycle. The drug content in the formulations ranged from 95.86% to 101.35% initially to 91.30% to 101.51% after the freeze-thaw cycle. Regarding the drug release, the results revealed the following cumulative percentages: GA-3% - 92.58% after 1.5 h; AE-3% - 51.60% after 6 h; GA + EA (1.5% = 1.5%) - 99.91% after 2 h; GA + EA- (1.5% = 1.5%) released 57.06%, after 6 h. Regarding toxicity, it was observed that the group treated with GA showed a lower survival rate of the larvae (40%) at the dose 3000 mg/Kg in the formulation. Following the same trend, in the acute lethal concentration (ALC50) test performed using Zophobas morio larvae, an ALC50 of 2191.51 mg/Kg was observed for GA at 48 h. Melanin analysis showed a decrease in concentrations of 30 mg/Kg in the GA group, 3 mg/Kg of EA and 3, 300, 3000 mg/Kg of GA + EA, of the pure drugs. In the groups with the drugs incorporated into the gel, there was a significant decrease (P < 0.05) in melanin in the vehicle (gel), at concentrations of 300 and 3000 mg/Kg of GA and EA. On the other hand, in the combination of GA + EA, a reduction was observed at concentrations of 3 and 30 mg/Kg when compared to the control group. Thus, the gel showed good quality as a pharmaceutical formulation for topical use and low toxicity, making it promising for use in skin therapies.

Yet another in vitro evidence that natural compounds introduced by diet have anti-amyloidogenic activities and can counteract neurodegenerative disease depending on aging.

A major issue in Alzheimer's disease (AD) research is to find some new therapeutic drug which decrease Amyloid-beta (Aß) aggregation. From a therapeutic point of view the major question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. Natural compounds are capable of binding to different targets implicated in AD and exert neuroprotective effects. Aim of this study was to evaluate the in vitro inhibition of Aß1-42 fibrillogenesis in presence of Gallic acid, Rutin, Melatonin and ProvinolsTM . We performed the analysis with Transmission and Scanning Electron Microscopy, and with X-ray microanalysis. Samples treated with Rutin, that arises from phenylalanine via the phenylpropanoid pathway, show the best effective result obtained because a significantly fibril inhibition activity is detectable compared to the other compounds. Melatonin shows a better inhibitory activity than ProvinolsTM and Gallic acid at the considered concentrations.

The anticancer/cytotoxic effect of a novel gallic acid derivative in non-small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients.

Gallic acid (GA) is a naturally occurring polyphenol with a strong antioxidant capacity. GA stimulates the apoptosis of cancer cells, thereby suppressing cancer cell invasion. However, the low oral permeability of GA limits its therapeutic use. In order to enhance the antioxidant capacity and oral permeability of GA, a series of compounds analogous to GA were synthesized: 4-methoxybenzenesulfonamide (MBS), 3,4-dimethoxybenzenesulfonamide (DMBS) and 3,4,5-trimethoxybenzenesulfonamide (TMBS). In the new compounds, hydroxyl groups were replaced with various numbers of methoxy groups (stronger electron-donating groups), to increase hydrophobicity and oral permeability compared to GA. In addition, the carboxylic group was replaced with a sulfonyl group (a stronger electron-withdrawing group), to increase the molecular polarity and antioxidative activities of the compounds. The cell counting kit-8 (CCK-8) assay was used to detect the effect of GA, MBS, DMBS, and TMBS on cell proliferation and apoptosis in peripheral blood mononuclear cells (PBMCs) from healthy individuals and non-small cell lung carcinoma A549 cells. Additionally, the comet assay was used to assess the genotoxicity of these compounds in PBMCs from healthy individuals, lung cancer patients, and A549 cells. Compared to untreated cells, TMBS reduced DNA damage more effectively than GA in PBMCs from lung cancer patients and healthy donors. Furthermore, in comparison to GA, TMBS was more cytotoxic in A549 cells. Moreover, TMBS was not cytotoxic in healthy PBMCs, suggesting that TMBS demonstrates therapeutic potential in cancer.

Ethyl gallate concurrent administration protects against acetaminophen-induced acute liver injury in mice: An in vivo and in silico approach.

Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti-inflammatory, and anti-microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP-induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N-acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor-α, interleukin-1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5-trihydroxybenzoic acid region. These effects of EG against APAP-induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti-inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication.