Gallic Acid Treatment Research Articles

REVERSAL OF CISPLATIN-INDUCED MEMORY IMPAIRMENT BY GALLIC ACID IN EXPERIMENTAL RAT MODEL

Objective: The objective of the study was to evaluate the protective effect of gallic acid on cisplatin-induced memory impairment (MI) in the rat model.
 Methods: Five groups of Wistar albino rats (n=6) were employed and the duration of the study was 22 days, excluding the pre-treatment period. Animals were pretreated with gallic acid for a period of 5 days and continued daily (200 mg/kg) for 22 days. The cisplatin (3 mg/kg) was given once in a week for 3 consecutive weeks to induce MI, whereas donepezil was used as standard. The evaluation was done by a change in body weight, memory activity by Morris water maze (MWM), locomotor activity by actophotometer, antioxidant activity by thiobarbituric acid reactive substance (TBARS), glutathione (GSH), and estimation of acetylcholinesterase (AChE) activity in brain homogenate.
 Results: Administration of cisplatin has induced MI by increasing in escape latency time, decrease in time spent in the target quadrant in the MWM task and it was reversed by gallic acid treatment. Decreased locomotor activity by cisplatin was also increased by gallic acid when tested by actophotometer. Cisplatin administration has induced oxidative stress by increasing TBARS and decreasing GSH levels. Gallic acid due to its proven antioxidant activity reversed the effects of cisplatin. The AChE level was significantly increased in the control group, whereas treatment groups have shown a decrease in AChE level.
 Conclusion: Gallic acid may serve as a primary agent to treat the cognitive impairment and oxidative stress associated memory dysfunctions. However, more extensive studies are needed before utilization in the clinical trial.

Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis

BackgroundThere are different treatments for breast cancer and melanoma that mostly have some side effects. One of the therapeutic strategies is the use of natural components. Phenol components are a class of antioxidants in plants that have many biological functions like anticancer effects. Gallic acid (GA) is a natural polyhydroxy phenolic compound and commonly found in various foods. In the present study, GA effects alone and in combination with low-level laser irradiation on human dermal fibroblast cell line (HDF), human non-tumorigenic breast epithelial cell line (MCF10A), breast cancer cell line (MDA-MB-231) and melanoma cancer cell line (A375) was under the investigation.MethodsThe normal and cancerous cell lines were exposed to 660 nm low-level laser with 3 J/cm2 for 90 s. Then, the cells were treated with different concentrations of GA for 24 h. In another study, the cell lines firstly were treated with GA and then exposed to low-level laser irradiation. The effects of GA and low-level laser on cell survival and apoptosis were examined using MTT assay, light microscopy, ROS production assay, fluorescence microscopy (AO/EB double staining) and flow cytometry.ResultsThe results showed that pre-treatment with low-level laser and then GA reduced the survival of breast cancer cells and melanoma more than the first treatment with GA and then low-level laser irradiation. Our findings showed that ROS production in cells treated with both low-level laser and GA was more than the cells treated with GA alone. The apoptosis and ferroptosis assays confirmed the MTT results which combination treatment with low-level laser and then GA increase the cell death probably via apoptosis and ferroptosis cell death mechanisms compared to GA alone.ConclusionsThis study suggests that low-level laser irradiation alone is not able to cause death in human normal and cancerous cells. Preirradiation followed by GA treatment did not change the cell viability in human normal significantly but reduces the cell survival of cancer cells more than GA alone.

Effects of gallic acid on rat testopathy following morphine administration: an experimental study

Introduction: Morphine (MOR) as a psychoactive agent in the opium family causes free radicals accumulation which leads to failure in spermatogenesis. Gallic acid (GA), a polyphenolic acid, is found in various plants with antioxidant, anti-fungal, anti-viral, and anti-allergic activities. The purpose of this study was to evaluate the effects of GA against MOR-induced damage to the reproductive parameter of rats. Methods: Sixty-four male Wistar rats (8 weeks, 220-250 g) were categorized into 8 groups by random (n=8/each); normal control and MOR control groups; GA groups (5, 10, 20 mg/kg) and MOR + GA groups (5, 10, 20 mg/kg). Treatments were administered intraperitoneally (i.p), daily for 4 weeks. The sperm parameters, spermatogenesis index (SI), total antioxidant capacity, testosterone level, and seminiferous tube diameter (STD) were assessed. Results: All sperm parameters reduced significantly in the MOR control group than to the normal control group (P < 0.01). All parameters were significantly improved in GA and GA + MOR treatment groups compared to the MOR control group (P < 0.01). Conclusion: MOR caused a detrimental effect on male reproductive parameters. Also, no significant modifications were observed in all doses of GA treatments in comparison with the normal control group. GA compensates the toxic effect of MOR on reproductive parameters. Hence, GA administration is beneficial in MOR users.

Effect of Pectin Coating Infused with Gallic Acid on the Quality and Shelf Life of Japanese Sea Bass (Lateolabrax japonicas) Fillets

In the present study, the effect of a pectin (PE) coating infused with gallic acid (GA) on the quality of fresh Japanese sea bass (Lateolabrax japonicas) fillets stored at 4 °C was evaluated over a 20-day period. PE or GA treatment alone and the PE infused with GA coating (PE-GA) all reduced microbial counts, with the PE-GA providing the greatest reduction. In general, samples of fish fillet treated with PE-GA had significantly lower levels of total volatile basic nitrogen, lipid oxidation, and total sulfhydryls, but higher Ca2+-ATPase activity during the storage period, compared with the untreated (control), PE-coated, and GA-treated fillets. Notably, PE-GA-treated samples also had the highest sensory quality rating. Results of the present study indicate that the PE-GA composite coating represents a promising food-grade biopreservative that can be used for maintaining the storage quality of fresh fish fillet.

Gallic acid attenuates thymic involution in the d-galactose induced accelerated aging mice.

Senescence is an inevitable and complicated phenomenon. Age-associated thymic involution increases the risk of infectious diseases, which results in the immunosenescence and leads to a poor immune function. d-galactose (d-gal) can cause damages that resemble accelerated aging in mice. Gallic acid (GA), as one of the natural phenolic compounds, has been demonstrated to act in antioxidant and anti-tumor effects. In this study, we explored the effects of GA in preventing the age-related thymic involution and the alterations of the forkhead box protein N1 (FoxN1) in d-gal induced accelerated aging mice. The accelerated aging mice model was established by intraperitoneal injection d-gal for eight weeks and given GA with 200, 250, 500 mg/kg body weight per day, respectively, for six weeks. It showed that the d-gal-treated mice developed structural changes in the thymi compared to normal control mice. With supplement of GA, the mice restored the normal thymic anatomy, including the thickening cortex compartment and clearer cortico-medullary junction. The d-gal-treated mice showed a severe reduction in the number of thymocytes, GA mice also displayed the increased numbers of CD4 + T cells through flow cytometric analysis. GA treatment increased the proliferative cells by BrdU incorporation assay and reduced the numbers of apoptotic cells with FITC-12-dUTP labeling (TUNEL). The expression of FoxN1 was also found increased in GA treated mice by immunohistochemistry and quantitative reverse transcriptase PCR (qRT-PCR). Taken together, our results suggested that the administration of GA opposed the involution of thymus via stimulation of FoxN1 expression and proliferation of cells in a dose-dependent manner.

Complexation between sodium caseinate and gallic acid: Effects on foam properties and interfacial properties of foam

The impact of gallic acid (GA) treatment on the adsorption behavior at the air/water interface and foam properties of sodium caseinate (SC) was investigated. The surface hydrophobicity and negative charge of SC were significantly decreased in bulk solution after interacting with GA. The combination between SC and GA was further confirmed by Fourier transform infrared spectrometer. Compared with SC, the foam stabilized by SC/GA complex (mass ratio of 1:1) showed excellent long-term stability. Moreover, the studies of air/water interfacial behavior demonstrated that the combination slightly decreased the interfacial activity of SC, but considerably increased its interfacial viscoelasticity, suggesting more stable of the air/water interface stabilized by SC/GA complex. Finally, the result of Lissajous plots analysis shows that the increase of GA content lead to the strain hardening occurs in the interface during compression and extension. This also proves that the addition of GA could improve the foam stability of the system.

A Role of Gallic Acid in Oxidative Damage Diseases: A Comprehensive Review

Gallic acid is a trihydroxybenzoic acid of plant metabolites widely spread throughout the plant kingdom. It has characteristics of the strong antioxidant and free radical scavenging activities, and can protect biological cells, tissues, and organs from damages caused by oxidative stress. This review aims to summarize the protective roles of gallic acid and the underlying pharmacological mechanisms in the pathophysiological process of the oxidative damage diseases, such as cancer, cardiovascular, degenerative, and metabolic diseases. The studies reviewed herein showed that the main therapeutic effects of gallic acid were attributed to its antioxidant properties. It modulated various signaling pathways through a wide range of inflammatory cytokines, and enzymic and nonenzymic antioxidants. However, the available data were limited to few studies assessing the treatment effects of gallic acid in human subjects to confirm its therapeutic outcomes. Therefore, the clinical trials were urgently needed to investigate the safety and efficacy of gallic acid treatment on human beings. The scientific data summarized in this review highlighted the therapeutic potentials of gallic acid for oxidative damage diseases. It could be developed as versatile adjuvant or therapeutically lead compound in future.

Evaluation of adaptive response in E. coli O157:H7 to UV light and gallic acid based antimicrobial treatments

Ability of bacteria to develop cross-protection to various stresses is well-known. However, exploration into cross-protection between conventional physiological stresses and emerging antimicrobial treatments is limited. Previously, we developed two new antimicrobial treatments based on a combined UV-A light and gallic acid (UVA + GA) treatment and enhanced antimicrobial action of gallic acid by UV-C exposure (UVC-GA) against Escherichia coli O157:H7. In this study, we investigated (a) whether prior exposure to sub-lethal stresses (heat, acid, osmotic and oxidation) can increase the resistance of E. coli O157:H7 towards these newly developed treatments, and (b) whether repeated exposure to these two treatments selects for E. coli O157:H7 sub-population resistant towards heat, acid, and oxidative challenge. Prior exposure to heat or acid stress increased (p < 0.05) the resistance of E. coli O157:H7 towards UVA + GA treatment, while osmotic stress increased (p < 0.05) their sensitivity to that treatment. Interestingly, only heat stress showed protective (p < 0.05) effect to subsequent UVC-GA treatment, while acid or osmotic stress increased (p < 0.05) the sensitivity. Prior exposure to oxidative stress had no effect (p > 0.05) on the sensitivity of the bacteria to either of the treatments. Repeated exposure to UVA + GA or UVC-GA treatment selected for a sub-population that demonstrated higher (p < 0.05) resistance towards these two treatments as well as heat or acid challenge. Further experiments showed that increased synthesis of enzymes such as superoxide dismutase and up-regulation of general stress response regulator were likely associated with the development of cross-protection. Thus, sub-lethal conditions encountered during food processing should be considered in the development and optimization of emerging non-thermal technologies.

Antidiabetic potential of gallic acid from Emblica officinalis: Improved glucose transporters and insulin sensitivity through PPAR-γ and Akt signaling

BackgroundNature has gifted a variety of vital phytochemicals having potential therapeutic application against various ailments. Emblica officinalis (E. officinalis), an ancient plant, has long been used as a remedy for diabetes and cardiovascular complications, and presence of abundant amount of gallic acid could be accountable for its medicinal potential. PurposeThe study was aimed to determine the in-vivo and in-vitro anti-diabetic potential of gallic acid and fruit juice of E. officinalis. Molecular mechanism of gallic acid as well as fruit juice of E. officinalis for anti-diabetic potential has also been revealed. Experimental study designAnti-diabetic potential of E. officinalis and gallic acid was evaluated in 3T3-L1 preadipocytes and various animal models like db/db mice and fructose administered rats. PPAR-γ expression and glucose translocation were observed using western blot and PCR techniques. ResultsTreatment of E. officinalis fruit juice and gallic acid facilitated their glucose homeostasis; improved insulin sensitivity; reduced obesity; abridged elevated blood pressure and declined cholesterol level, and also induced adipogenesis in 3T3-L1 adipocytes. Mechanistically, treatment increased expression of PPAR-γ through activation of C/EBPs and simultaneously increased Glut4 translocation in 3T3-L1 adipocytes. Moreover, gallic acid treatment increased insulin sensitivity through activation of Akt rather than AMPK signaling pathway while fruit juice of E. officinalis showed dual activation, Akt and AMPK as well. ConclusionThese findings reveal the role of gallic acid in E. officinalis mediated antidiabetic potential, and delineate the upregulation of pAkt, PPAR-γ and Glut4 in gallic acid mediated antidiabetic activity, thus providing potential therapy for diabetes and related disorders.

Synergistic antihyperglycaemic effect of combination therapy with gallic acid and andrographolide in streptozotocin-induced diabetic rats

Abstract Previous studies had reported on the antidiabetic effect of gallic acid and andrographolide, as monotherapy, in diabetic rats. However, studies on the combination effect of gallic acid and andrographolide in treating diabetes are lacking. Hence, the objective of this study was to investigate the antihyperglycaemic activity of combined gallic acid and andrographolide in streptozotocin-induced diabetic rats compared to single compound treatment. Diabetes was induced with streptozotocin (40 mg/kg, intraperitoneally) in male Sprague Dawley rats. After 7 days, all rats were divided into 8 groups as follows: normal control and diabetic control groups given distilled water, diabetic groups treated with gallic acid (10 or 20 mg/kg), andrographolide (5 or 10 mg/kg), or both in 2:1 combination ratio of gallic acid:andrographolide (10:5 or 20:10 mg/kg). All treatments were given orally, once daily for 15 consecutive days. Non-fasting blood glucose, food and water intake were measured weekly. On day 14, an oral glucose tolerance test was performed. Our results showed that the combination treatment of gallic acid and andrographolide synergistically reduced blood glucose compared to single compound treatment, with higher synergistic effect and favourable dose reduction at higher combination dose. Furthermore, the combination treatment significantly improved glucose tolerance, with significantly reduced area under the curve in diabetic rats. The combination treated diabetic group also demonstrated normalization of their daily food and water intake. In conclusion, our results indicated that the combination therapy at 2:1 combination ratio of gallic acid:andrographolide demonstrated synergistic hypoglycaemic activity with favourable dose reduction in experimental diabetic rats.

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice.

The present study has been investigated the role of gallic acid (GA) in paclitaxel-induced neuropathic pain. The neuropathic pain was developed with paclitaxel (PT: 2 mg/kg, i.p.) administration in mice. GA (20 and 40 mg/kg) and pregabalin (PreG: 5 mg/kg) were administered intravenously for 10 consecutive days. The neuralgic sensations were investigated by assessing various pain tests like acetone drop, pinprick, plantar, tail flick, and tail pinch test. Mice pain behaviors were evaluated on 0, 4th, 8th, 12th and 16th days. The levels of sciatic nerve thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide anion, calcium, myeloperoxidase (MPO), and TNF-α were estimated. Treatment of GA and PreG attenuate PT induced thermal &mechanical hyperalgesia and allodynia symptoms along with the reduction of TBARS, total calcium, TNF-α, superoxide anion, and MPO activity levels; and decreased GSH level. Therefore, it has been concluded that GA has potential neuroprotective actions against PT induced neuropathic pain due to it's anti-oxidant, anti-inflammation and regulation of intracellular calcium ion concentration.

A holistic view of gallic acid-induced attenuation in colitis based on microbiome-metabolomics analysis.

Gallic acid (GA), a plant phenol found in fruits and vegetables, has been recently reported to attenuate ulcerative colitis (UC). However, the mechanism of GA in UC remains unknown. In this study, we investigated the therapeutic effects of GA on UC from the perspective of gut microbiota and supervised the metabolic alterations in vivo with 1H NMR-based metabolomics, which can provide a holistic view to understand the functions of GA in UC. Rats with dextra sulfate sodium (DSS)-induced colitis were rectally administrated with GA (6 mg kg-1) for 8 consecutive days. 16S gene sequencing was performed on feces samples to obtain bacterial community information. Urine and feces samples were analyzed with 1H NMR spectroscopy, and short chain fatty acids (SCFAs) in feces and colon contents were detected with gas chromatography. Our results showed that UC syndromes in the GA group were significantly attenuated. The microbial alterations in the DSS group were characterized by a decrease of probiotic bacteria, such as Lactobacillaceae and Prevotellaceae, and an increase of some pathogenic species, mainly in the Firmicutes and Proteobacteria phyla. GA treatment could modulate the microbiota composition towards a similar proportion to the control group. Metabolic data further revealed that the GA-induced metabolic changes focus on increasing carbohydrate metabolism (gluco-related metabolism) and bile acid (BA) metabolism and decreasing amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are by-products of interactions between the host and the microbiota. These findings demonstrate GA-induced alterations in metabolic and bacterial profiles in DSS-colitis, providing new insight into the attenuation of GA in UC.

Determination of three active components in Euphorbia humifusa willd. Using high-performance liquid chromatography with diode-array detection and autophagy and apoptosis analysis of normal rat kidney and hela cells

Background: Euphorbia humifusa Willd. (EH) is a kind of Chinese medicinal plant belonging to the family Euphorbiaceae, which is traditionally used for influenza, jaundice, hepatitis B virus, hypotension, inflammation, etc. In a modern study, active ingredients of EH reported to exhibit antioxidant, anticancer, and other properties. However, there are few reports showing that EH and its active compounds have inhibitory effects on cervical cancer through autophagy and apoptosis. Objective: To evaluate the anticervical cancer activity of EH and its main active ingredient Gallic acid (GA) by studying on autophagy and apoptosis of normal rat kidney (NRK) and HeLa cell lines, respectively. Materials and Methods: GA, kaempferol (KA), and quercetin (QU) are the main active compounds of EH. Identification and quantification of three substances from four batch samples obtained from four areas in Xinjiang were analyzed by high-performance liquid chromatography with diode-array detection. The potent effects of EH on anticervical cancer were investigated through autophagy and apoptosis in HeLa and NRK cells with varying concentrations of extracts and active compound GA treatment. The antiproliferation activity against HeLa cells was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Autophagy and apoptosis in NRK and HeLa cells were observed by laser scanning confocal microscope. Quantitative data of apoptosis were estimated by Hoechst staining and Annexin-V binding assay using flow cytometry. The expression levels of autophagy-related protein (LC3 and P62) were subjected to western blot. Moreover, the autophagic vacuoles and other ultrastructures of cells were observed under transmission electron microscopy. Results: The contents of GA, KA, and QU were measured as 2.3342–3.4688, 0.4636–1.5922, and 0.9349–3.1500 mg/g, respectively. We used different concentrations of GA and the extracts of EH to treat with the line of cells, respectively. The best concentration of GA, water, and ethanol extracts inducing autophagy was 25 μg/ml, 10 mg/ml, and 10 mg/ml, respectively. The autophagy mediated with EH induced the accumulation of autophagosome, and even resulted in apoptosis. Conclusion: From our study, these results indicated that EH and GA may induce both autophagy and apoptosis in NRK and HeLa cells. The activity we studied on autophagy and apoptosis of HeLa cells may provide a new foundation for cervical cancer therapy or other related applications. Abbreviations used: EH: Euphorbia humifusa Willd.; HPLC-DAD: High-performance liquid chromatography with diode-array detection; NRK: Normal rat kidney; GA: Gallic acid; FC: Flow cytometry; LSCM: Laser scanning confocal microscope; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; TEM: Transmission electron microscopy; KA: Kaempferol; QU: Quercetin; LC3: The light chain 3; DMEM: Dulbecco's Modified Eagle's medium; FBS: Fetal bovine serum; DMSO: Dimethyl sulfoxide; PBS: Phosphate-buffered saline; PI: Propidium iodide; IC50: Half-maximal inhibitory concentration; BFA: Bafilomycin A1.

Polysaccharides and polyphenols in sea buckthorn leaf tea have synergistic impact on studied colonic strains in vitro and bacteria in vivo

Present research on prebiotics focuses on either polysaccharides or polyphenols. This study compared the individual and combined impact of polysaccharide, quercetin, and gallic acid (GA) treatment on three human faecal strains. In vitro pure culturing and correlation analysis confirmed that the growth of both beneficial microbe B. longum subsp. longum (0.695, 0.205: R2, slope, respectively) and pathogenic C. perfringens (0.712, 0.085: R2, slope, respectively) increased due to polysaccharide treatment, and only GA treatment would inhibit C. perfringens (0.789, –0.165: R2, slope, respectively) growth. In vivo studies also revealed that genome copies of Bifidobacterium increased and C. perfringens decreased in the faeces, when a blend of the three nutrients rather than single polysaccharide or polyphenols were fed to rats. These data suggested that combined prebiotic treatment improved human faecal strain composition better than single treatment.

Effect of gallic acid on chronic restraint stress-induced anxiety and memory loss in male BALB/c mice.

Objective(s):Long-term exposure to stress leads to memory deficits and certain mood disorders such as depression and anxiety. We aimed to study the effect of gallic acid (GA) on chronic restraint stress (CRS) induced anxiety and memory deficits in male BALB/c mice.Materials and Methods:Ninety male BALB/c mice were assigned to nine groups including caged control (CC): food-water deprived (FWD), under chronic restraint stress (CRS), CRS+ gallic acid (5, 10, and 20 mg/kg), and gallic acid (5, 10, and 20 mg/kg). Behavioral assays were performed after 21 days of daily treatment with CRS and GA. Serum and brain levels of malondialdehyde (MDA) and total antioxidant capacity (TCA) and serum corticosterone level were also measured. Results:Treatment of CRS mice with GA significantly improved passive avoidance memory in the shuttle box and ameliorated anxiety-like behaviors in the elevated plus maze (EPM) and open filed test (OFT). GA treatment significantly reduced elevated levels of serum and brain MDA and increased brain TCA. CRS and GA did not affect serum corticosterone levels. Treatment of healthy mice with GA had some adverse effects and induced some anxiety and oxidative stress. Conclusion:GA exerted protective effects against stress-induced mood and memory deficit disorders.

The Antioxidant Gallic Acid Inhibits Aflatoxin Formation in Aspergillus flavus by Modulating Transcription Factors FarB and CreA.

Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in Aspergillus flavus in a dose-dependent manner. Global expression analysis (RNA-Seq) of gallic acid-treated A. flavus showed that 0.8% (w/v) gallic acid revealed two possible routes of aflatoxin inhibition. Gallic acid significantly inhibited the expression of farB, encoding a transcription factor that participates in peroxisomal fatty acid β-oxidation, a fundamental contributor to aflatoxin production. Secondly, the carbon repression regulator encoding gene, creA, was significantly down regulated by gallic acid treatment. CreA is necessary for aflatoxin synthesis, and aflatoxin biosynthesis genes were significantly downregulated in ∆creA mutants. In addition, the results of antioxidant enzyme activities and the lipid oxidation levels coupled with RNA-Seq data of antioxidant genes indicated that gallic acid may reduce oxidative stress through the glutathione- and thioredoxin-dependent systems in A. flavus.

The antioxidant gallic acid induces anxiolytic-, but not antidepressant-like effect, in streptozotocin-induced diabetes.

The physiopathology of anxiety or depression related to diabetes is still poorly understood. The treatment with antidepressant drugs is a huge challenge due to theirs adherence low rate and many adverse effects. Thus, the seeking for a better treatment for these associated diseases is of utmost importance. Given that the oxidative stress in different tissues occurs in diabetes and anxiety or depression as well, the antioxidant gallic acid becomes an interesting compound to be investigated. Thus, the effects of long-term treatment with gallic acid (0, 10, 20 and 40mg/kg; gavage) were evaluated in diabetic (DBT) animals submitted to the elevated plus-maze (EPM), the light-dark transition (LDT) tests and modified forced swim test (mFST). Also, indirect parameters of oxidative stress, lipid peroxidation (LPO) and reduced glutathione (GSH) levels were evaluated in the hippocampus (HIP) and prefrontal cortex (PFC). The results showed that DBT animals presented a decrease in the spent time in the open arms, in the end arm exploration and head dips when evaluated in the EPM test; moreover, a decrease in the spent time in the lit compartment of LDT test was observed, suggesting an anxiogenic-like behavior. During the mFST, an increase in the mean counts of immobility and a decrease in the mean counts of swimming and climbing were observed, indicating a depressive-like behavior. These aversive behaviors were more pronounced when compared to normoglycemic (NGL) animals and streptozotocin-treated animals that not become DBT. In addition, DBT rats showed an increase in the oxidative stress parameters in the HIP and PFC that was reversed by the gallic acid treatment (lowest dose - 10mg/kg), i.e., the treatment decreased the elevated LPO levels and increased the reduced GSH in the HIP and PFC. Also, gallic acid treatment was able to produce an anxiolytic-like effect in the EPM and LDT tests, but not antidepressant-like effect in the FST. Taken together, the results suggest that the antioxidant/neuroprotective effect of gallic acid treatment in HIP and PFC of DBT animals may be essential to the anxiolytic-like effect.

Effects of gallic acid on signaling kinases in murine macrophages and immune modulation against Brucella abortus 544 infection in mice

In this study, we investigated the effects of gallic acid (GA) in intracellular signaling within murine macrophages and its contribution to host immunity during Brucella infection. In vitro analysis revealed that GA treatment decreased F-actin content and suppressed p38α phosphorylation level. In vivo analysis showed that GA treatment reduced inflammation and proliferation of Brucella in spleens of mice in comparison to PBS treatment yielding a significant protection unit. For the analysis of immune response, the uninfected GA-treated mice showed increased production of IFN-γ and MCP-1, and the Brucella-infected GA-treated mice showed elevated levels of IL-12p70, TNF, IFN-γ, MCP-1, IL-10 and IL-6 in comparison to negative and positive control groups, respectively. These findings demonstrate the therapeutic effects of GA against Brucella infection through interference on intracellular signaling pathway, induction of cytokine production and protection from bacterial proliferation in spleens of mice.

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells.

Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

Effect of gallic acid on purinergic signaling in lymphocytes, platelets, and serum of diabetic rats

Diabetes Mellitus (DM) is associated with an increased susceptibility to various infections, which might be attributed to changes in immune response owing to chronic hyperglycemia. Nucleoside triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase, and adenosine deaminase (ADA) are important enzymes involved in the generation of anti-aggregant and anti-inflammatory microenvironments. The aim of this study was to evaluate the effect of gallic acid (GA) on the hematological parameters and ectonucleotidase activities in platelets, lymphocytes, and serum of diabetic rats. Experimental rats were categorized into 4 groups: (i) control -saline, (ii) control - GA, (iii) diabetic -saline, and (iv) diabetic - GA. One week after induction of DM using streptozotocin (65 mg/kg), GA (30 mg/kg) or saline was orally administered to the rats for 21 days. Our results demonstrated that the concentration of mean corpuscular hemoglobin was decreased, whereas that of red cell distribution was increased in the diabetic group, however, GA could revert these alterations. Moreover, in diabetic rats, GA reverted the increase in ATP and ADP hydrolysis and ADA activity in lymphocytes, and it prevented the increase in NTPDase and ADA activities in platelets. A decrease in ATP hydrolysis and an increase in ADP and AMP hydrolysis were observed in the serum of diabetic rats; however, GA treatment could solely revert changes in ATP hydrolysis. Our study suggests that GA exhibits beneficial effects on immuno- and thrombo-regulatory responses in DM and that these effects may be related to the modulation of purinergic signaling.