Administration Of Gallic Acid Research Articles

Investigation of the Anti-diabetic and Anti-lipid Peroxidative Properties of Gallic Acid in Diabetic Rats

Diabetes mellitus is a chronic non-communicable disease that occurs due to insulin deficiency or reduced function in the body. Therefore, the scientific investigation of herbal plants and their effectiveness is essential. It has been shown that gallic acid has hypoglycemic properties. In this study, the anti-diabetic and anti-lipid peroxidation properties of gallic acid were investigated. For this purpose, Streptozotocin was injected intraperitoneally into male rats at a dose of 60 mg/kg to induce type I diabetes. Seven days after Streptozotocin injection, blood samples were taken and rats with serum glucose levels higher than 250 mg/dL were considered diabetic. The rats were divided into 4 groups. Two groups of diabetic rats received either water or gallic acid at a dose of 40 mg/kg, and two groups of normal rats received either water or gallic acid at 40 mg/kg dose. The treatment period for all groups was 8 weeks. After the end of the period, blood samples were taken from the rats under fasting conditions. The collected blood samples were analyzed for serum biochemical factors (glucose, cholesterol, triglycerides, High-density lipoprotein, and creatinine) using spectrophotometry with the respective kits, and the level of lipid peroxidation in red blood cells was measured. The administration of gallic acid at a dose of 40 mg/kg (8 weeks) significantly reduced serum levels of glucose, triglycerides, cholesterol, alanine aminotransferase, aspartate aminotransferase, very low-density lipoprotein, low-density lipoprotein, and creatinine, while significantly increasing serum levels of high-density lipoprotein. Additionally, the level of Malondialdehyde in red blood cells was decreased in the diabetic group receiving gallic acid compared to the diabetic control group, and in normal rats receiving gallic acid at a dose of 40 mg/kg (8 weeks), it had no significant effect on serum factors and had no toxicity.

Gallic Acid Alleviates Injury of Intestine Induced by Escherichia Coli: Protective Role of Metalloproteinase and Antioxidants on Small Intestine In-vivo

Background: Escherichia coli (E. coli) is a common pathogen that can cause significant morbidity and mortality in hospitalized patients. The aim of this study was to investigate the effects of gallic acid (GA) on a mice infected with of E. coli enteritis and evaluate the serum levels of interleukin-6 (IL-6) and matrix metalloproteinase (MMP)-9, as well as any histopathological changes before and after exposure. Materials and Methods: Forty Swiss male mice were divided into four groups: Group I (negative control), Group II (received oral GA, 80 mg/kg/b.wt), Group III (orally inoculated with E. coli, 1×107 CFU, for four days), and Group IV (received oral GA, 80 mg/kg/b.wt, for 10 days after E. coli inoculation). Serum was collected to assess IL-6 and MMP-9 levels. Intestinal samples were examined for antioxidant parameters, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase. Histopathology and immunohistochemistry were performed. Results: Group III exhibited significantly higher IL-6 and MMP-9 levels compared to the other groups (P<0.001). Antioxidant activity in the intestine, measured by SOD and GSH-Px, was lower in Group III compared to Group I. Conversely, Group IV showed significant improvements in biochemical, histopathological, and immunohistochemical outcomes, alongside reduced intestinal damage caused by E. coli. Conclusion: This study demonstrates that E. coli infection in mice increases IL-6 and MMP-9 levels while decreasing intestinal antioxidants. Concurrent administration of GA significantly improves outcomes, suggesting its potential as a therapeutic remedy for E. coli-induced intestinal damage. Furthers research is imperative to determine the underlying pathways by which GA exerts its beneficial outcomes.

Gallic acid counteracts tartrazine-induced testicular dysfunction in rats: biochemical, histopathological and ultrastructural evidences

BackgroundTartrazine (Tz) is one of the most commonly used colorants incorporated in the food manufacturing. Its toxicity is derived from metabolic byproducts representing health hazards to consumers. Gallic acid (GA) is known for its redox stabilizing, anti-apoptotic, and cytoprotective characteristics. Therefore, the aim of this study is to explore the possible defensive effect of GA against Tz-induced testicular dysfunction. To achieve this objective, 18 male Wistar adult rats were randomly and equally categorized into three groups for 30 days. The control group received no treatment. Tz at a dose of 30 mg/kg BW was administered to the Tz group. The Tz + GA group received GA at a dose of 200 mg/kg BW in concurrent with the previously described Tz dosage. Both Tz and GA were supplemented orally once daily by a stomach tube.ResultsThe marked decline in luteinizing hormone, follicle stimulating hormone, testosterone, and estradiol 17beta confirmed deviation in pituitary–gonadal axis of Tz-exposed rats. Imbalances in plasma redox equilibrium were evident, characterized by a notable increase in malondialdehyde and nitric oxide levels, along with a decrease in reduced glutathione and total antioxidant capacity. Deteriorations in histopathological features, fibrosis in testicular tissue, abnormalities in Sertoli cell, and up-regulation in caspase-3 were observed. Conversely, GA administration successfully reversed these issues.ConclusionThe ability of GA to counteract toxicological molecular targets in Tz-exposed testes is believed to be achieved through the restoration of oxidant/antioxidant balance and the prevention of the apoptotic cascade.

GSK-3β/Notch-1 Activation Promotes Radiation-Induced Renal Damage: The Role of Gallic Acid in Mitigation of Nephrotoxicity.

Despite the therapeutic advances in treating malignancies, the efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate the role of gallic acid (GA) in modifying the hazardous renal cytotoxicity induced by acute exposure to radiation. The MTT test was used to evaluate the viability of Vero cells exposed to 2 Gy gamma radiation with or without incubation of GA. In an in vivo model, male Wistar rats were divided into four experimental groups (n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 mg/kg, i.p.) + IRR. Based on the MTT toxicity assay, from 0 and up to 5 μM dosages of GA did not demonstrate any cytotoxicity to Vero cells. The optimal GA dose that could protect the cells from radiation was 5 μM. Furthermore, GA exerted a protective effect from gamma radiation on renal tissue as indicated by corrected renal functions, decreased LDH level in serum, and balanced oxidative status, which is indicated by decreased tissue contents of NOx and TBARS with a significant increase of reduced GSH. These outcomes were inferred by the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The overall molecular impact of radiation in damaging the renal tissue may be explained by modifying the upstream AKT activity and its downstream targets GSK-3β/Notch-1. Here, we concluded that the anticipated adverse reaction in the course of radiation exposure could be protected by daily administration of GA.

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.

Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin.

To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Gallic Acid Protects from Sepsis-Induced Acute Lung Injury.

Sepsis, a leading global cause of morbidity and mortality, involves multiple organ dysfunction syndromes driven by free radical-mediated processes. Uncontrolled inflammation in early sepsis stages can lead to acute lung injury (ALI). Activated leukocytes generate reactive oxygen species, contributing to sepsis development. Gallic acid, a phenolic compound, is known for its antimicrobial properties. This study aims to observe gallic acid's protective and restorative effect on the lungs in an experimental sepsis model. Male Wistar albino rats were subjected to a feces intraperitoneal injection procedure (FIP) to induce sepsis. Four groups were formed: normal control, FIP alone, FIP with saline, and FIP with gallic acid. Gallic acid was administered intraperitoneally at 20 mg/kg/day. Blood samples were collected for biochemical analysis, and computed tomography assessed lung tissue histopathologically and radiologically. Gallic acid significantly decreased malondialdehyde, IL-6, IL-1β, TNF-α, CRP levels, oxidative stress, and inflammation indicators. Lactic acid levels decreased, suggesting improved tissue oxygenation. Histopathological examinations revealed reduced lung damage in the gallic-acid-treated group. Computed tomography confirmed lower lung density, indicating less severe inflammation. Arterial blood gas analysis demonstrated improved oxygenation in gallic-acid-treated rats. Gallic acid exhibited anti-inflammatory and antioxidant effects, reducing markers of systemic inflammation and oxidative stress. The findings support its potential to protect against ALI during sepsis. Comparable studies underline gallic acid's anti-inflammatory properties in different tissues. Early administration of gallic acid in sepsis models demonstrated protective effects against ALI, emphasizing its potential as an adjunct therapy to mitigate adverse outcomes. The study proposes gallic acid to reduce mortality rates and decrease the need for mechanical ventilation during sepsis-induced ALI.

Gallic acid attenuates metastatic potential of human colorectal cancer cells through the miR-1247-3p-modulated integrin/FAK axis.

Colorectal cancer (CRC) exhibits highly metastatic potential even in the early stages of tumor progression. Gallic acid (GA), a common phenolic compound in plants, is known to possess potent antioxidant and anticancer activities, thereby inducing cell death or cell cycle arrest. However, whether GA reduces the invasiveness of CRC cells without inducing cell death remains unclear. Herein, we aimed to investigate the antimetastatic activity of low-dose GA on CRC cells and determine its underlying mechanism. Cell viability and tumorigenicity were analyzed by MTS, cell adhesion, and colony formation assay. Invasiveness was demonstrated using migration and invasion assays. Changes in protein phosphorylation and expression were assessed by Western blot. The involvement of microRNAs was validated by microarray analysis and anti-miR antagonist. Our findings showed that lower dose of GA (≤100 μM) did not affect cell viability but reduced the capabilities of colony formation, cell adhesion, and invasiveness in CRC cells. Cellularly, GA downregulated the cellular level of integrin αV/β3, talin-1, and tensin and diminished the phosphorylated FAK, paxillin, Src, and AKT in DLD-1 cells. Microarray results revealed that GA increased miR-1247-3p expression, and pretreatment of anti-miR antagonist against miR-1247-3p restored the GA-reduced integrin αV/β3 and the GA-inhibited paxillin activation in DLD-1 cells. Consistently, the in vivo xenograft model showed that GA administration inhibited tumor growth and liver metastasis derived from DLD-1 cells. Collectively, our findings indicated that GA inhibited the metastatic capabilities of CRC cells, which may result from the suppression of integrin/FAK axis mediated by miR1247-3p.

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.

Gallic Acid Attenuates Cardiovascular and Hematological Complications in Vincristine Treatment via Hydroxyl Radical Scavenging and Endogenous Antioxidant Stimulation in Male Wistar Rats

The menace of cancer and the nightmare of complications of cancer chemotherapy have driven researchers to explore simple but efficient combination therapy that includes antioxidants, in cancer therapy. The ability of gallic acid to correct the toxic complication of Vincristine was investigated. Twenty adult male rats of the Wistar strain were grouped into four, randomly, consisting of five rats each. The untreated control (group A) was given only distilled water, groups B and C 0.025 mg/kg Vincristine sulfate intraperitoneally once a week for two weeks. Group C rats were thereafter administered 100 mg/kg gallic acid daily by gastric gavage for 14 days. At 14 days, blood pressure and ECG were measured in the rats, then blood samples were obtained via the retrorbital venous plexus for determination of haematological parameters and plasma biochemistry. They were then euthanized through cervical dislocation, under ether anaesthesia, and liver, kidneys, heart, and brain samples were collected, weighed, and stored for determination of marker of oxidative stress in the post mitochondrial fractions of each organ. Results of the study showed that rats in group B had hypertension as evidenced by elevated diastolic and systolic as well as mean arterial pressure while QT interval and corrected QT were slightly elongated. They also had lowered RBC, WBC, and granulocyte counts. Markers of oxidative stress, GSH, and SOD were also depleted while H2O2 generation increased in this group, whereas all the observed anomalies were corrected in the group C rats that were administered both Vincristine and gallic acid. This study further showed that Vincristine, at normal recommended therapeutic dosage is toxic, causing anaemia, panleucopenia, and cardiovascular anomalies via oxidative stress and generation of hydroxyl radicals. These were however corrected by concurrent administration of gallic acid

Apoptotic Effect of Gallic Acid via Regulation of p-p38 and ER Stress in PANC-1 and MIA PaCa-2 Cells Pancreatic Cancer Cells.

Pancreatic cancer (PC) is currently recognized as the seventh most prevalent cause of cancer-related mortality among individuals of both genders. It is projected that a significant number of individuals will succumb to this disease in the forthcoming years. Extensive research and validation have been conducted on both gemcitabine and 5-fluorouracil as viable therapeutic options for PC. Nevertheless, despite concerted attempts to enhance treatment outcomes, PC continues to pose significant challenges in terms of achieving effective treatment alone through chemotherapy. Gallic acid, an endogenous chemical present in various botanical preparations, has attracted considerable attention due to its potential as an anticancer agent. The results of the study demonstrated that gallic acid exerted a decline in cell viability that was dependent on its concentration. Furthermore, it efficiently suppressed cell proliferation in PC cells. This study observed a positive correlation between gallic acid and the production of reactive oxygen species (ROS). Additionally, it confirmed the upregulation of proteins associated with the protein kinase-like endoplasmic reticulum kinase (PERK) pathway, which is one of the pathways involved in endoplasmic reticulum (ER) stress. Moreover, the administration of gallic acid resulted in verified alterations in the transmission of mitogen-activated protein kinase (MAPK) signals. Notably, an elevation in the levels of p-p38, which represents the phosphorylated state of p38 MAPK was detected. The scavenger of reactive oxygen species (ROS), N-Acetyl-L-cysteine (NAC), has shown inhibitory effects on phosphorylated p38 (p-p38), whereas the p38 inhibitor SB203580 inhibited C/EBP homologous protein (CHOP). In both instances, the levels of PARP have been successfully reinstated. In other words, the study discovered a correlation between endoplasmic reticulum stress and the p38 signaling pathway. Consequently, gallic acid induces the activation of both the p38 pathway and the ER stress pathway through the generation of ROS, ultimately resulting in apoptosis. The outcomes of this study provide compelling evidence to support the notion that gallic acid possesses considerable promise as a viable therapeutic intervention for pancreatic cancer.

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 Ameliorates Cognitive Impairment Caused by Sleep Deprivation through Antioxidant Effect.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

Gallic acid attenuates the Chronic construction injury of sciatic nerve induced neuropathic pain in mice

Gallic acid (GA) is one of the natural flavonoids and it is known to protect the neuronal system from various endogenous neurodegenerative processes. The present study is focused on evaluating the role of GA in chronic construction injury (CCI) of sciatic nerve-induced neuropathic pain. The test compound i.e., gallic acid (20 and 40mg/kg), and reference compound i.e., pregabalin (PrG: 5mg/kg) were administered intravenously for 10 consecutive days. The sciatic nerve injury-induced neuralgic sensations were assessed with multiple test methods like acetone drop, pinprick, plantar, tail-flick, and tail pinch tests at different time points i.e., 0, 4th, 8th, 12th, and 16th days. The biochemical level changes i.e., thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide anion, calcium, myeloperoxidase (MPO), and tumor necrosis factor–α (TNF-α) were estimated in sciatic nerve samples. The administration of GA and PreG was shown a significant ameliorative effect against the CCI-induced pain response in a dose-dependent manner. Moreover, it also attenuated the tissue biochemical changes. The observed effects of GA were similar to reference drug PreG treated groups. Hence, GA has neuroprotective and pain relief effects against the CCI-induced neuralgia. It may be due to its natural free radical scavenging; regulation of inflammatory proteins; expression of antioxidant proteins, reduction of intracellular free calcium, and prevention of neuroinflammatory actions.

Effect of Gallic Acid Pretreatment and SGK1 Enzyme Inhibition on Cardiac Function and Inflammation in a Rat Model of Ischemia-Reperfusion Injury.

Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 inhibitor on cardiac function after I/R. This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 inhibitor, the heart was perfused with the SGK1 inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated. The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, lactate dehydrogenase, and troponin-I (P < 0.05). The results indicated that administration of gallic acid with the SGK1 inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation.

Preventive Effect of Indian Gooseberry (Phyllanthus emblica L.) Fruit Extract on Cognitive Decline in High-Fat Diet (HFD)-Fed Rats.

Methylglyoxal (MG)-derived advanced glycation end products (AGEs) directly bind to the receptor for advanced glycation end products (RAGE), subsequently exacerbating obesity and obesity-induced cognitive decline. Indian gooseberry (Phyllanthus emblica L.) fruit has antiobesity properties. However, the underlying mechanism by which Indian gooseberry fruit prevents obesity-induced cognitive decline remains unclear. This study aims to investigate the preventive effect of a water extract of Indian gooseberry fruit (WEIG) and its bioactive compound gallic acid (GA) on the obesity-induced cognitive decline through MG suppression and gut microbiota modulation in high-fat diet (HFD)-fed rats. Trapping MG, WEIG, and GA significantly ameliorate fat accumulation in adipose tissue and learning and memory deficits. Mechanistically, WEIG and GA administration effectively reduces brain MG and AGE levels and subsequently reduces insulin resistance, inflammatory cytokines, MDA production, and Alzheimer's disease-related proteins, but increases both antioxidant enzyme activities and anti-inflammatory cytokine with inhibiting RAGE, MAPK, and NF-κB levels in HFD-fed rats. Additionally, WEIG and GA supplementation increases the relative abundances of Bacteroidetes, Gammaproteobacteria, and Parasutterella, which negatively correlate with MG, inflammatory cytokine, and Alzheimer's disease-related protein expressions. This novel finding provides a possible mechanism by which WEIG prevents obesity-induced cognitive decline through the gut-brain axis.

Protective effects of crocin and gallic acid on the liver damage induced by methylglyoxal in male mice: role of inflammatory factors.

This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by the administration of gallic acid (GA), crocin (Cr), and metformin (MT) in the liver. MG is produced naturally through various physiological processes, but high levels of MG cause inflammation in hepatocytes. Normal liver function is essential for maintaining glucose homeostasis. Gallic acid and crocin can reduce inflammation. This experiment was done in 5 weeks. 50 male NMRI mice were randomly divided into 5 groups (n=10): 1) Control, 2) MG (600 mg/Kg/d, p.o.), 3) MG+GA (30 mg/kg/day, p.o.), 4) MG+Cr (60 mg/kg/day, p.o.), 5) MG+MT (150 mg/kg/day, p.o.). After one week of habituation, MG was administered for four weeks. Gallic acid, crocin, and metformin were administered in the last two weeks. Biochemical and histologic evaluations were assessed after plasma collection and tissue sample preparation. Gallic acid and crocin-received groups significantly reduced fasting blood glucose, total cholesterol, triglyceride levels, and elevated insulin sensitivity. Administration of MG exerted a marked increase in the levels of hepatic enzymes. Treatment with gallic acid, crocin, and metformin significantly decreased them. The altered levels of inflammatory factors in the diabetic group were significantly improved in the diabetic-treated groups. High levels of steatosis and red blood cells (RBCs) accumulation in the MG group markedly recovered in other treated mice. Harmful effects of accumulated MG in the liver of diabetic mice were effectively attenuated by using gallic acid and crocin.

Hepatoprotective effect of gallic acid against type 2-induced diabetic liver injury in male rats through modulation of fetuin-A and GLP-1 with involvement of ERK1/2/NF-κB and Wnt1/β-catenin signaling pathways.

Gallic acid is a phenolic compound with biological and pharmacological activities. Therefore, our study aimed to examine whether gallic acid has a beneficial effect against type 2-induced diabetic hepatic injury in rats and attempt to discover its possible intracellular pathways. Adult male rats were subdivided into six groups: Control, DM (diabetes mellitus), GA (gallic acid)+DM, DM+GA, DM+MET (metformin) and DM+GA+MET. Type 2 diabetes mellitus (T2DM) induced a significant increase in the blood glucose, HOMA-IR, liver enzymes, fetuin-A, hepatic triglycerides content with diminished serum insulin and hepatic glycogen content associated with impairment of cellular redox balance. Administration of gallic acid successfully restored all these alterations which was confirmed by marked improvement of the histopathological changes of the liver. Significantly, gallic acid increased the expression of glucagon-like peptide-1 (GLP-1) immunoreactive cells in the terminal ileum with negative correlation observed between fetuin-A and GLP-1 cells. Furthermore, our results discovered that gallic acid could diminish the DM-induced hepatic damage via upregulated hepatic mRNA expression of GLUT-4, Wnt1 and β-catenin with inhibitory effects on the elevated expression of ERK1/2/NF-κB. In conclusion, this study suggests that gallic acid provides a significant protection against T2DM-mediated liver injury. The use of gallic acid with traditional anti-diabetic drug enhanced its efficiency compared with traditional drug alone.

Gallic and ascorbic acids supplementation alleviate cognitive deficits and neuropathological damage exerted by cadmium chloride in Wistar rats

Cadmium is a highly neurotoxic heavy metal that interferes with DNA repair mechanisms via generation of reactive oxygen species. The potentials of polyphenols and antioxidants as effective protective agents following heavy metal-induced neurotoxicity are emerging. We therefore explored the neuroprotective potentials of gallic and ascorbic acids in CdCl2-induced neurotoxicity. Seventy-two Wistar rats were divided into six groups. Group A received distilled water, B: 3 mg/kg CdCl2, C: 3 mg/kg CdCl2 + 20 mg/kg gallic acid (GA), D: 3 mg/kg CdCl2 + 10 mg/kg ascorbic acid (AA), E: 20 mg/kg GA and F: 10 mg/kg AA orally for 21 days. Depression, anxiety, locomotion, learning and memory were assessed using a battery of tests. Neuronal structure and myelin expression were assessed with histological staining and immunofluorescence. The Morris Water Maze test revealed significant increase in escape latency in CdCl2 group relative to rats concurrently treated with GA or AA. Similarly, time spent in the target quadrant was reduced significantly in CdCl2 group relative to other groups. Concomitant administration of gallic acid led to significant reduction in the durations of immobility and freezing that were elevated in CdCl2 group during forced swim and open field tests respectively. Furthermore, GA and AA restored myelin integrity and neuronal loss observed in the CdCl2 group. We conclude that gallic and ascorbic acids enhance learning and memory, decrease anxiety and depressive-like behavior in CdCl2-induced neurotoxicity with accompanying myelin-protective ability.

Evaluation the Protective Role of Gallic Acid on Cardiac Arrhythmias Induced by Oxidative Stress in Rat Exposure to Particulate Matters

Introduction: Particulate matter (PM) increases the risk of heart disorders. Gallic acid (GA) with strong antioxidant properties has shown an effective role in reducing the complications of various diseases. The aim of this study was to evaluate the protective effect of Gallic acid in preventing cardiac arrhythmias due to exposure to particulate matter. Methods: In this study, 40 rats were placed in 4 groups including: control, Particulate matter (5 mg/kg), Gallic acid (30 mg/kg) and particulate matter + Gallic acid. The rats were anesthetized, blood pressure was measured with a tail cuff, and the lead Π of electrocardiogram was examined to record the prevalence of cardiac arrhythmias. Oxidative stress factors were evaluated in blood samples of all groups. Data were analyzed by SPSS software version 16 and ANOVA statistical test. Results: The results showed the occurrence of cardiac arrhythmia in rats exposed to particulate matter compared to the control group. Gallic acid significantly reduced the incidence of ventricular arrhythmias ventricular tachycardia (P=0.006), ventricular fibrillation (P=0.0005) and premature ventricular contraction (P=0.0041) in the particulate matter group. The Malondialdehyde levels in the particulate matter group showed a significant increase (P=0.0049) that this increase caused oxidative stress and reduced the levels of superoxide dismutase (P=0.00031) and catalase (P=0.0019) in the particulate matter group compared to the control group. The Gallic acid administration improved the levels of antioxidant enzymes. Conclusion: The results of this study show that Gallic acid as a natural antioxidant agent could prevent cardiac complications caused by exposure to particulate matter.