Gallic Acid Treatment Research Articles

Gallic acid enhances GVL effects of T cells without exacerbating GVHD after haematopoietic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for acute myeloid leukaemia (AML), predominantly due to its potent graft-versus-leukaemia (GVL) effect. However, leukaemia relapse remains a major obstacle to the success of allo-HSCT. In this study, we demonstrated that gallic acid (GA), a natural dietary compound, can enhance T-cell-mediated GVL effects both invitro and invivo. GA-treated T cells exhibited increased activation and elevated secretion of cytotoxic cytokines, leading to the apoptosis of AML cells in co-culture systems invitro. In a non-irradiated leukaemia mouse model, we showed that GA treatment prolonged the survival of leukaemic mice and reduced leukaemia cell infiltration. Further analysis revealed that GA treatment increased T-cell activation and tumour necrosis factor-α secretion. Moreover, integrated transcriptomic and proteomic analyses indicated that GA augments T-cell-mediated GVL effects through the activation of the MAPK and NF-κB pathways. Blocking these pathways individually diminished the protective effect of GA in AML model mice. Importantly, GA administration did not accelerate graft-versus-host disease (GVHD) progression in a mouse model. In conclusion, our study revealed that GA can enhance the GVL effects of T cells without exacerbating GVHD, offering insights into its potential to improve outcomes for patients after HSCT.

Gallic Acid Alleviates Glucolipotoxicity-Induced Nephropathy by miR-709-NFE2L2 Pathway in db/db Mice on a High-Fat Diet.

Type 2 diabetes mellitus (T2DM) has become a major global issue, with diabetic nephropathy (DN) ranking as one of its most serious complications. The involvement of microRNAs (miRNAs) in the progression of T2DM and DN is an area of active research, yet the molecular mechanisms remain only partially elucidated. Gallic acid (GA), a naturally occurring polyphenolic compound found in various plants such as bearberry leaves, pomegranate root bark, tea leaves, and oak bark, has demonstrated antioxidant properties that may offer therapeutic benefits in DN. The study aimed to investigate the therapeutic potential of GA in mitigating kidney fibrosis, oxidative stress and inflammation, within a glucolipotoxicity-induced diabetic model using db/db mice. The mice were subjected to a high-fat diet to induce glucolipotoxicity, a condition that mimics the metabolic stress experienced in T2DM. Through microarray data analysis, we identified a significant upregulation of renal miR-709a-5p in the diabetic mice, linking this miRNA to the pathological processes underlying DN. GA treatment was shown to boost the activity of including catalase, essential antioxidant enzymes, glutathione peroxidase and superoxide dismutase, while also reducing lipid accumulation in the kidneys, indicating a protective effect against HFD-induced steatosis. In vitro experiments further revealed that silencing miR-709a-5p in MES-13 renal cells led to a reduction in oxidative stress markers, notably lowering lipid peroxidation markers, and significantly boosting the activity of antioxidant defenses. Additionally, NFE2L2, a crucial transcription factor involved in the antioxidant response, was identified as a direct target of miR-709a-5p. The downregulation of miR-709a-5p by GA suggests that this polyphenol mitigates glucolipotoxicity-induced lipogenesis and oxidative stress, potentially offering a novel therapeutic avenue for managing diabetic fatty liver disease and DN. Our findings indicate that GA exerts a protective effect in DN by downregulating miR-709a-5p, thereby alleviating oxidative stress through the suppression of NFE2L2. The results highlight the potential of GA and NFE2L2-activating agents as promising therapeutic strategies in the treatment of DN.

Gallic acid regulates primary root elongation via modulating auxin transport and signal transduction.

Gallic acid is an important secondary metabolite in plants, with great value in medicine, food, and chemical industry. However, whether and how this widely existing natural polyphenolic compound affects the growth and development of plants themselves remains elusive. In this study, we revealed that exogenous application of gallic acid has a dual effect on the elongation of primary root in Arabidopsis. While lower concentrations of gallic acid slightly stimulate primary root growth, excessive gallic acid profoundly reduces primary root length and root meristem size in a dose-dependent manner, probably via suppressing cell division in root meristem as indicated by CYCB1;1::GUS. Moreover, as suggested by the DR5::GFP line analysis and confirmed by the LC-MS assay, auxin contents in root tips were dramatically decreased upon excessive gallic acid treatment. Additional application of IAA partially rescued the shortened primary root and root meristem upon excessive gallic acid treatment, suggesting that auxin is required for excessive gallic acid-caused root growth inhibition. Then, we further revealed that excessive gallic acid down-regulated the expression of auxin transporters PIN1, PIN2, PIN3, and PIN7, and triple mutant pin1 pin3 pin7 exhibited a reduced sensitivity to gallic acid treatment. Meanwhile, excessive gallic acid decreased the degradation of AXR3/IAA17 protein as revealed by HS::AXR3NT-GUS reporter line. Auxin signaling mutant tir1 afb2 afb3 and axr3-3 were also less sensitive to excessive gallic acid treatment in terms of primary root length and root meristem size. Taken together, these findings suggested that excessive gallic acid inhibits primary root growth by modulating auxin transport and signaling in Arabidopsis.

The Protective Effect of Gallic Acid Against Bisphenol A-Induced Ovarian Toxicity and Endocrine Disruption in Female Rats.

Purpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNFα], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1β], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNFα, COX-2, IL-1β, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants.

Synthesis of non-modified near-infrared carbon dots for hypochlorite detection and cell membrane imaging

Devising carbon dots with long wavelength emission (red light or near infrared), high selectivity and good bio-compatibility is critical in fluorescence detection and imaging, but achieving this goal remains a great challenge. Herein, near-infrared emissive carbon dots (NIR-CDs) with obvious emission characteristic of 653 nm were synthesized through hydrothermally treatment of toluidine bule and gallic acid. Noticeably, the NIR-CDs exhibited excellent selectivity and sensitivity to hypochlorite (ClO−), and the limit of detection is as low as 42.7 nM. The selective recognition reaction between ClO− and the surface functional groups of NIR-CDs inhibits the fluorescence from NIR-CDs. The quenching mechanism was confirmed by fluorescence lifetime decays, FT-IR spectroscopy and UV–vis absorption spectra. More remarkably, the NIR-CDs have rich hydrophilic groups showed lower cytotoxicity, excellent bio-compatibility and specific cell membrane localization ability. The established spectrofluorometric method based on NIR-CDs has been used to determination of ClO− level in tap water sample, the recoveries were 97.7 %–103.3 %. In addition, the NIR-CDs also has been successfully applied for the imaging of cell membrane. The study provides a novel idea for developing NIR ClO− probe as well as cell membrane localization probe based on CDs, which present bright prospects in real water samples monitoring and cell membrane imaging.

Effect of Gallic Acid on PTZ-induced Neurotoxıcıty, Oxidative Stress and Inflammation in SH-SY5Y Neuroblastoma Cells

Aim: Human neuroblastoma cell lines are widely used to elucidate the cellular and molecular mechanisms of neurotoxicants and to facilitate the prioritization of in vivo testing. Pentylenetetrazole (PTZ) is a tetrazole derivative. Although PTZ is the most commonly used chemical to create an in vivo and in vitro epilepsy (EP) model, its mechanism of action in neuronal cells has not been fully elucidated. Gallic acid (GA) has broad biological properties such as antioxidant, anti-microbial, and anti-inflammatory activities. This study aimed to investigate the effect of GA on PTZ-induced neurotoxicity in neuroblastoma cells. Methods: For the study, four groups were formed from SH-SY5Y neuroblastoma cells as control (C), GA (100 μM), PTZ (30 μM), and PTZ+GA. In the study, total antioxidant and oxidant status (TAS and TOS), inflammatory cytokines (TNF α, IL 1β, and IL 6), lipid peroxidation levels as malondialdehyde (MDA), glutathione peroxidase (GSHPx), and glutathione (GSH) levels in the SH-SY5Y neuroblastoma cells were determined. Results: The results showed that PTZ treatment caused neurotoxicity in the neuroblastoma cell line and increased TOS, TNF α, IL 1β, IL 6, and MDA levels while decreasing TAS, GSH, and GSHPx levels. This situation improved with GA treatment. Conclusion: As a result, it was determined that GA treatment showed a protective effect in the PTZ-induced neural toxicity model in SH-SY5Y human neuroblastoma cell lines.

Modification of hordein by gallic acid in ethanol-free environments: Impact of covalent and non-covalent interactions on structure, physicochemical properties and self-assembly

The objectives of this study were to modify hordein with gallic acid (GA) in alcohol-free media and to compare the impact of covalent and non-covalent binding on the properties of hordein. Covalent hordein-GA complexes (H-GA) and non-covalent hordein/GA complexes (H/GA) were distinguished by molecular weight, free sulfhydryl groups and free amino groups. Isothermal titration calorimetry (ITC) demonstrated that physical mixing induced non-covalent binding of GA to hordein via hydrogen bonding and hydrophobic interactions, with a lower binding efficiency than covalent ones. Both complexation types led to a structural shift of hordein toward disorder, while grafting of oligomeric GA and alkaline treatment resulted in lower surface hydrophobicity and higher antioxidant activity of H-GA compared to H/GA. The nanoparticles assembled from H-GA had smaller particle sizes and higher physical stability than those formed from H/GA. The results of this study may provide new insights into the modification of hordein by polyphenols.

Effect of Indian gooseberry extract on improving methylglyoxal-associated leptin resistance in peripheral tissues of high-fat diet-fed rats.

Increased leptin resistance and methylglyoxal (MG) levels are observed in obese patients. However, whether MG deposits contribute to leptin resistance, oxidative stress, and inflammation in peripheral tissues remains unclear. In addition, the edible fruit of Indian gooseberry (Phyllanthus emblica L.) contains abundant bioactive components such as vitamin C, β-glucogallin (β-glu), gallic acid (GA), and ellagic acid (EA). Water extract of Indian gooseberry fruit (WEIG) and GA has been shown to improve cognitive decline by suppressing brain MG-induced insulin resistance in rats administered a high-fat diet (HFD). Accordingly, this study investigated the functions of WEIG and GA in inhibiting MG-induced leptin resistance, oxidative stress, and inflammation in the peripheral tissues of HFD-fed rats. The results showed that MG, advanced glycation end products (AGEs), and leptin resistance accumulation in the liver, kidney, and perinephric fat were effectively restored by elevated glyoxalase-1 (Glo-1) activity after WEIG and GA administration comparable to that of alagebrium chloride (positive control) treatment in HFD-fed rats. Furthermore, WEIG and GA supplementation increased adiponectin and antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase) and decreased inflammatory cytokines (IL-6, IL-1β, TNF-α) in the peripheral tissues of HFD-fed rats. In conclusion, these findings demonstrated that MG may trigger leptin resistance, oxidative stress, and inflammation in peripheral tissues, which could be abolished by WEIG and GA treatment. These results show the potential of P. emblica for functional food development and improving obesity-associated metabolic disorders.

Gallic Acid and Doxorubicin Treatment HeLa cell lines by MTT assay

Objective: Cervical cancer, as it is medically known, occurs in the cells in the lower part of the uterus called the cervix and is one of the most common gynecological cancers in the world. Hormonal and genetic factors play a major role in the development of endometrial cancer. Chemotherapeutic drugs are very effective in treatment. However, serious side effects and the development of drug resistance limit the use of these drugs. In our study, the cytotoxic effects of Gallic acid (GA), which is found in many popular foods, on HeLa cells were investigated.&#x0D; Methods: In our study, different doses of GA and Dox were applied to the cells for 48 hours and cytotoxicity levels were determined by the MTT method. All results were analyzed statistically.&#x0D; Results: It was observed that cytotoxicity by MTT was at the highest level in the GA and Dox administered group. IC50 was determined and it was found that GA IC50 was 239.2 and Dox IC50 was 137.6.&#x0D; Conclusion: As a result of the study, it was shown that the highest cytotoxic effect occurred with GA application and this may support Dox application with a synergistic effect.&#x0D; Keywords: Servics cancer, Gallic acid, Doxorubicin, MTT

Elucidating the Molecular Mechanism by Which Gallic Acid Alleviates Oxidative Stress and Inflammatory Response of Acrylamide-Induced Renal Injury in a Rat Model

This study investigates the molecular effects of Acrylamide (ACR)-induced kidney damage and the potential protective role of Gallic acid (GA). Forty male rats were divided into five groups: Control, ACR, ACR+GA50, ACR+GA100, and GA100. The ACR groups received a daily oral dose of 50 mg/kg, while GA groups received 50 or 100 mg/kg oral doses for 14 consecutive days. On the 15th day, the animals were euthanized, and kidney samples were collected. The MDA, GSH, SOD, GPx, and CAT oxidative stress parameters were measured. The renal inflammatory response was evaluated by measuring the level of TNF-α, IL-1β, IL-6, NF-κB, COX-2, and IL-10. The downstream pro-apoptotic signaling pathway was resolved by measuring the levels of p38 MAPK and p53. The ACR induced renal oxidative stress with aggravated lipid peroxidation as revealed by the reduction in the levels GSH, SOD, GPx, and CAT of antioxidants while over-increase in the level of MDA, respectively. The levels of IL-1β, IL-6, NF-kB, COX-2 pro-inflammatory mediators as well as the p38 MAPK and p53 pro-apoptotic intermediates were further elevated. This increase in inflammatory response was met with marked decrease in anti-inflammatory IL-10 level. However, GA treatments- in dose dependent manner- had been demonstrated to effectively mitigate oxidative stress and reduce inflammatory responses, while also enhancing the cellular anti-inflammatory defense mechanisms. The GA can be considered as a novel protective antioxidant, anti-apoptotic drug against ACR-induced nephrotoxic insult. Further study should be performed to estimate the exact effective dose.

Gallic acid modulates oxido-inflammatory response in acrylamide-induced hepato-renal toxicity

Dietary and environmental exposure to acrylamide (ACR) has been linked with liver and kidney illnesses, cardiopulmonary diseases, and neurological problems. Nevertheless, gallic acid (GA) is a potent polyphenolic compound with many therapeutic attributes. This present research explored the protective effect of GA against ACR hepato-renal toxicity. GA treatment was initially for 7 days followed by subsequent co-administration with ACR for a further 21 days. Twenty-four male Wistar rats were randomly distributed into six groups: Group I (control) was orally administered normal saline (2 ml/kg b.wt/day), Groups II and III were orally administered GA only (20 and 40 mg/kg b.wt/day respectively), Group IV received 20 mg/kg b.wt/day ACR only, Groups V, and VI were both given 20 mg/kg b.wt/day ACR co-administered with GA (20 and 40 mg/kg b.wt/day)The level of malondialdehyde (MDA), glutathione (GSH), and the activity of glutathione peroxidase (GPx) were evaluated in kidney and liver tissues while alanine amino transaminase (ALT), aspartate amino transaminase (AST), alkaline phosphatase (ALP), TNF-α and IL-6 were assayed in the serum. Treatment of GA remarkably improved ACR-induced perturbation of the biochemical and inflammatory indicators. The levels of MDA, urea, creatinine, TNF-α, and IL-6 as well as the activities of ALT, and AST were significantly increased while GSH levels and GPx activity were significantly decreased in ACR-exposed rats.Taken together, GA treatment exhibited antiinflammatory and antioxidant protective properties in ACR-induced hepato-renal toxicity.

Anti-influenza A (H1N1) virus effect of gallic acid through inhibition of virulent protein production and association with autophagy.

Influenza remains one of the most serious infectious diseases. Gallic acid is one of the most common and representative phenolic acids found in various plants. This is an interesting subject to explore how gallic acid could inhibit H1N1 influenza virus infection by reducing the production of virulent proteins and interrupting autophagy machinery for influenza virus replication on the host cell. Cellular viability was assessed by XTT assay. The inhibitory effects on the H1N1 influenza virus were assessed by hemagglutination assay, plaque assay, and qRT-PCR. Western blot analysis was used for detecting protein levels of M1, M2, NP, LC3B, and beclin-1. Autophagy activity was demonstrated by acridine orange staining assay. The result demonstrated that there was no cytotoxic effect of gallic acid on A549 cells, and gallic acid could restore the cellular viability of H1N1 influenza virus-infected A549 cells within the experimental concentration treatment. Moreover, gallic acid could effectively restrain viral activity of the H1N1 influenza virus. After the treatment of gallic acid, the production of virulent H1N1 influenza virus proteins, that is, M1, M2, and NP protein were reduced. As for autophagic mechanism, both of the LC3B II conversion and the level ratio of LC3B II to LC3B I were notably decreased. The acridine orange staining assay also revealed decreased accumulation of autophagosomes in H1N1 influenza virus-infected cells. In conclusion, gallic acid suppresses H1N1 influenza viral infectivity through restoration of autophagy pathway and inhibition of virulent M1, M2, and NP protein production.

Gallic acid exerts protective effects in spinal cord injured rats through modulating microglial polarization

BackgroundSpinal cord injury (SCI) is a highly traumatic injury that causes mechanical damage to the spinal cord. Our study aimed to investigate whether gallic acid has protective effects against SCI injury. MethodsAdult male rats were subjected to contusive spinal cord injuries. For behavioural evaluation, the rats were given gallic acid by i.p. injection at the doses of 10, 50 or 100 mg/kg immediately after SCI once daily for consecutive 28 days. Behavioral tests were used to evaluate locomotor functions, mechanical sensitivity and nerve conduction functions. For biochemical experiments, the rats were randomly divided into three groups: sham group, SCI group and SCI+gallic acid group. The rats in the SCI+gallic acid group were given gallic acid at the dose of 100 mg/kg immediately after SCI once daily for consecutive 14 days. The levels of inflammatory factors were evaluated. ResultsGallic acid treatment could improve locomotive and sensory function and reduce the functional impairments in SCI rats. The effects were more effective with increasing gallic acid dose. The levels of M1 markers (inducible nitric oxide synthase and cyclooxygenase-2) were decreased in gallic acid-treated SCI rats, whereas the levels of M2 markers (arginase 1 and cluster of differentiation 206) were increased in response to gallic acid administration. Gallic acid treatment resulted in a significant reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokine levels. ConclusionGallic acid enhances the recovery in SCI rats by regulating microglial polarization. The underlying mechanism may involve the promotion of M2 polarization and the suppression of M1 polarization in microglia.

Inhibition of GATA3, ABCB1, and TYR by gallic acid: A real-world approach to uncovering a preventive agent against oral squamous cell carcinoma development

ObjectiveThis study aimed to the efficacy of gallic acid (GA) as a prospective prophylactic agent against the onset of oral squamous cell carcinoma (OSCC). MethodsWe conducted bioinformatic analyses to identify the molecular targets of GA. Subsequently, we employed the 4NQO-induced animal model to evaluate the therapeutic potential of GA in OSCC. ResultsOur analysis unveiled that only three genes, ABCB1, GATA3, and SERPINE1, were associated with survival outcomes in OSCC patients. Reduced expressions of ABCB1 and GATA3 correlated with hazard ratios of 1.53 and 2.06, respectively, for mortality, while elevated SERPINE1 expression carried a 1.42-fold increased risk of death in OSCC patients. Molecular docking simulations underscored the robust affinity between GA and these genes, revealing binding energies of −6.0 kcal/mol for ABCB1, − 6.1 kcal/mol for GATA3, and −5.9 kcal/mol for SERPINE1. Furthermore, GA treatment demonstrated statistically significant reductions in the histopathological grade of 4NQO-induced lesions (p = 0.006) and mitigated liver (p < 0.001) and kidney (p < 0.001) toxicity associated with 4NQO exposure. ConclusionThe current study highlights GA as a promising contender for OSCC prevention. Mainly, GA targets critical genes such as ABCB1, GATA3, and SERPINE1, substantially impacting patient survival. Furthermore, GA administration mitigates 4NQO-induced toxicity, indicating its potential to improve animal survival by reducing lesion severity. These findings carry significant implications for OSCC research and potential clinical applications.

Gallic acid treatment protects intestinal tissue against ischaemia-reperfusion.

This study aimed to investigate the protective effects of gallic acid (GA) in the rat intestine against ischaemia-reperfusion (IR) injury. Thirty male Wistar albino rats with a mean weight of 200-250 g were used. Animals were categorized into the sham, IR, and IR+GA groups. Ischaemia of the intestine was induced for 3 h by occluding the superior mesenteric artery (SMA) and then left for 3 h of reperfusion. In the IR+GA group, after ischaemia induction, 50 mg/kg GA was orally administered to the animals. Blood samples were collected for biochemical assays. Intestinal tissues were excised for histopathologic and immunohistochemical processing. Malondialdehyde (MDA) levels were increased, and catalase (CAT) and glutathione (GSH) levels were decreased in the IR group compared to the sham group. After GA treatment, MDA levels decreased and CAT and GSH levels increased in the GA-treated group compared to the IR group. In the sham group, normal intestinal histology was observed. In the IR group, the villi structures were completely degenerated. In the IR+GA group, histology was improved after GA treatment. In the sham group, the caspase-3 reaction was generally negative in the epithelium and glands. In the IR group, the caspase-3 reaction increased in apoptotic bodies and inflammatory cells. The caspase-3 reaction was negative in goblet cells and the epithelium. A moderate caspase-3 reaction was observed in the IR+GA group. The beclin-1 reaction was negative in epithelial cells and goblet cells in villi in the sham group. In the IR group, the beclin-1 reaction was positive in the degenerated villi. An intense beclin-1 reaction was also observed in some inflammatory cells. After GA treatment, the beclin-1 reaction was positive in a few cells. In general, moderate beclin-1 positivity was observed. Gallic acid, with its antioxidative effect, inhibited the apoptotic pathway (caspase-3) through beclin-1 regulation.

Effect of Gallic Acid Treatment on Hepatic Tissue in Ischemia-Reperfusion

Aim: Hepatic IR occurs in many clinical conditions such as liver injury, liver hemorrhage and shock, surgical resection, and transplantation. In our study, it is aimed to investigate whether gallic acid (GA) can be used for hepatoprotective purposes, histopathologically.&#x0D; Study Desıgn: 24 Wistar albino male rats were divided into 3 groups (n:8). Surgical procedures were done under general anesthesia. A 4 cm midline abdominal incision were opened to observe hepatoduodenal ligament. The portal vein and hepatic artery was closed with a rubber band and silk suture, and ischemia was performed for 60 minutes. The suture was opened and hepatic reperfusion was performed for 6 hours. 50 mg/kg Gallic Acid was administered to the rats in this group by intraperitoneal route once a day for 14 days.&#x0D; Results: Normal histology of lvier was observed with regular vena centralis, endothelial cells, hepatocytes and sinusoid. In IR group, blood vessels were dilated and congested with cell infiltrations. Hepatocytes were degenerated with irregular sinusoides and hyperplasic Kupfer cells. IR+GA group, mononuclear cell infiltration continued with thickening of the basement membrane of the vessels. Vacuolated hepatocyte was observed. GA treatment alleviasted the pathologies occurred due to IR injury.&#x0D; Conclusion: It was thought that the cellular damage in the inflammation signal, which started as a result of the cessation of blood flow after ischemia-reperfusion injury, affects the classical lobule of the liver especially around the vena, and may cause necrotic changes by increasing cell apoptosis due to functional nutritional deficiency.&#x0D; Keywords: liver, ischemia, reperfusion, gallic acid, histology

Effect of Gallic Acid on Distant Organ Stomach in Intestinal Ischemia Reperfusion Injury

Aim: To examine the effects of gallic acid (GA) in the stomach in rats undergoing intestinal ischemia/reperfusion (IR) with Beclin -1 immunostaining.&#x0D; Material-Metod: 24 male Wistar albino rats were divided into control, IR and IR+GA groups. For the IR protocol, 60 minutes of ischemia and reperfusion were applied. The small intestines of the rats in the control group were removed by laparotomy and the abdomen was closed without applying anything else. Ischemia and reperfusion was applied to the superior mesenteric artery (SMA) for 60 minutes with a clamp in rats in the IR group. The blood flow was stopped with a clamp on the SMA of the rats in the IR+GA group and ischemia was applied for 60 minutes. 50 mg/kg gallic acid was given intraperitoneally to the animals, 60 minutes of reperfusion was performed, and the abdomen was closed. The stomach tissues were placed in paraffin blocks after routine histological follow-ups. Five micrometer-thick sections were taken from the paraffin blocks and stained with Hematoxylin-eosin and Beclin-1 immunostaining.&#x0D; Results: In the IR group, degeneration of gastric folds, apoptosis of epithelial cells and degeneration of lamina muscularis were observed. In the IR + GA group, gastric folds improved, but cell infiltration in the lamina propria and degeneration in the muscular layer were observed. Beclin-1 expression was positively observed in the surface epithelial cells and gastric glands in the control group. In the IR group, it was observed that the gastric folds were positive on the surface cells and negative in the submucosa, while in the IR + GA group, it was intensely expressed in the gastric epithelium and gastric glands.&#x0D; Conclusion: By increasing the expression of beclin-1, GA treatment induced autophagy in gastric mucosal cells, triggered the destruction of damaged cells and provided restoration of the mucosal layer.&#x0D; Keywords: Beclin-1, gallic acid, apoptosis

Effects of gallic acid on gingival wounds.

Our aim in this study was to investigate the effect of Gallic acid (GA) on gingival tissue injury. Twenty rats were categorized into two groups. In the burn group, an excisional wound area was created by removing a 4 mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In the Burn+gallic acid group, 1.2 mg/ml GA was administered as irrigation for 1 week. Animals were sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels were measured. Hematoxylin Eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostaining was applied to tissues. MDA and MPO levels increased, and GSH, epithelization, FGF and EGF expression levels were decreased. Gallic acid treatment improved these scores. Degenerated gingival epithelium, disintegrity in epithelial and connective tissue fibers, edema and inflammatory cells were observed in the burn group. Gallic acid treatment after burn improved the pathologies. After burn injury, FGF and EGF activity was increased in Gallic acid-treated groups. We suggest that GA has the potential for better healing outcomes in oral wounds. GA seems to have promising therapeutic efficacy in enhancing oral wound healing.

Biochemical analysis, photosynthetic gene (psbA) down-regulation, and in silico receptor prediction in weeds in response to exogenous application of phenolic acids and their analogs.

Chemical herbicides are the primary weed management tool, although several incidences of herbicide resistance have emerged, causing serious threat to agricultural sustainability. Plant derived phenolic acids with herbicidal potential provide organic and eco-friendly substitute to such harmful chemicals. In present study, phytotoxicity of two phenolic compounds, ferulic acid (FA) and gallic acid (GA), was evaluated in vitro and in vivo against three prevalent herbicide-resistant weed species (Sinapis arvensis, Lolium multiflorum and Parthenium hysterophorus). FA and GA not only suppressed the weed germination (80 to 60% respectively), but also negatively affected biochemical and photosynthetic pathway of weeds. In addition to significantly lowering the total protein and chlorophyll contents of the targeted weed species, the application of FA and GA treatments increased levels of antioxidant enzymes and lipid peroxidation. Photosynthetic gene (psbA) expression was downregulated (10 to 30 folds) post 48 h of phenolic application. In silico analysis for receptor identification of FA and GA in psbA protein (D1) showed histidine (his-198) and threonine (thr-286) as novel receptors of FA and GA. These two receptors differ from the D1 amino acid receptors which have previously been identified (serine-264 and histidine-215) in response to PSII inhibitor herbicides. Based on its toxicity responses, structural analogs of FA were also designed. Four out of twelve analogs (0.25 mM) significantly inhibited weed germination (30 to 40%) while enhancing their oxidative stress. These results are unique which provide fundamental evidence of phytotoxicity of FA and GA and their analogs to develop cutting-edge plant based bio-herbicides formulation in future.

Microalga Chlorella sp. extract induced apoptotic cell death of cholangiocarcinoma via AKT/mTOR signaling pathway

Cancer is the leading cause of death worldwide. Drug resistance and relapse after current standard treatments frequently occur; thus, alternative and effective treatments are required. Algae and cyanobacteria are abundant organisms that serve as bioresources of nutrients/metabolites, which are attractive sources of numerous bioactive compounds for drug discovery. In the present study, we, therefore, investigated anti-cancer activities of crude polysaccharide and ethanolic extracts from Chlorella sp., Sargassum spp., and Spirulina sp. against cell lines of five top-leading cancers including lung cancer (A549), cervical cancer (Hela), breast cancer (MCF7), hepatocellular carcinoma (Huh7), and cholangiocarcinoma (CCA; KKU213A). Only ethanolic extracts of Chlorella sp. showed consistent inhibition of growth of all cancer cell types. CCA was the most sensitive to Chlorella sp. ethanolic extract with CC50 of 277.4, 400.5, and 313.4 µg/mL for KKU055, KKU100, and KKU213A cells, respectively. Flow cytometric analysis demonstrated that CCA cell death was triggered via apoptosis pathway in accompany with lowering procaspase-3, -8, and -9 and increasing caspase enzymatic activity in addition to reducing anti-apoptosis Bcl-2 protein. Interestingly, the treatment of the extract at 400 µg/mL greatly inhibited the AKT/mTOR survival signaling as evidenced by significant reduction of phosphorylated-AKT and phosphorylated-mTOR proteins. The presence of reported bioactive compounds, gallic acid, and lutein, were confirmed in Chlorella sp. extract by high-performance liquid chromatography. Gallic acid and lutein treatment caused a significant reduction of KKU055, KKU100, and KKU213A cell viability. This study demonstrated the anti-cancer effect of Chlorella sp. ethanolic extract to promote cancer cell death via inhibition of AKT/mTOR pathway.