Gallic Acid Treatment Research Articles

Gallic acid regulates immune response in a mouse model of rheumatoid arthritis.

Previous studies revealed that gallic acid (GA) exerts anti-inflammation and immuno-regulatory properties. This study aims to explore the pharmacological activities of GA in collagen-induced arthritis (CIA) mouse model. Male DBA/1J mice were used to construct the CIA model. The mice were administrated with GA for 3 weeks. Clinical arthritis scores and hind paw volume were evaluated over the experimental period. qPCR and Western blot analysis were used to determine the levels of matrix metallopeptidases (MMPs) and cytokines. In addition, flow cytometry was used to measure the populations of Th17 and Treg cells. ELISAs were used to determine the cytokines in the serum and ankle joint tissues. Treatment of GA (40 and 80 mg/kg/d) reduced clinical arthritis scores and hind paw volume in the CIA mouse model. Besides, treatment of GA reduced the overexpression of MMPs and modulated the dysregulation of inflammation-related cytokines. Flow cytometry showed that treatment of GA decreased the population of Th17 cells, and increased the population of Treg cells, as supported by treatment of GA regulated the Th17/Treg-related cytokines. GA attenuates symptoms in the CIA mouse model by anti-inflammation and regulating Th17/Treg cell imbalance.

Gallic Acid Improves Comorbid Chronic Pain and Depression Behaviors by Inhibiting P2X7 Receptor-Mediated Ferroptosis in the Spinal Cord of Rats.

Ferroptosis is an inflammatory programmed cell death process that is dependent on iron deposition and lipid peroxidation. The P2X7 receptor not only is involved in the pain process but also is closely related to the onset of depression. Gallic acid (3,4,5-trihydroxybenzoic acid), which is naturally found in a variety of plants, exhibits anti-inflammatory, antioxidant, and analgesic effects. This study established a rat model with the comorbidity of chronic constrictive injury (CCI) plus chronic unpredictable mild stress (CUMS) to explore the role and mechanism of gallic acid in the treatment of pain and depression comorbidity. Our experimental results showed that pain and depression-like behaviors were more obvious in the chronic constriction injury (CCI) plus chronic unpredictable mild stimulation (CUMS) group than they were in the sham operation group, and the P2X7-reactive oxygen species (ROS) signaling pathway was activated. The tissue iron concentration was increased, and mitochondrial damage was observed in the CCI plus CUMS group. These results were alleviated with gallic acid treatment. Therefore, we speculate that gallic acid inhibits the ferroptosis of the spinal microglia by regulating the P2X7-ROS signaling pathway and relieves the behavioral changes in rats with comorbid pain and depression.

DOES GALLIC ACID HAVE A POTENTIAL REMEDIAL EFFECT IN EXPERIMENTAL CORROSIVE BURN INJURY TO THE ESOPHAGUS?

Gallic acid, acting as an antioxidant, anti-precipitant and cytoprotective agent, was used as a possible remedial natural component for treating experimentally induced esophageal burn. Wistar rats (n=24) were divided into three groups. Control group was given 1 mL 0.9% NaCl. Experimental esophageal burn was induced with 1 mL 40% NaOH application to the esophagus in groups 2 and 3. Gallic acid® (20 mg/kg) was administered to the treated group via oral gavage for 10 days. Removed tissues were fixed and paraffin blocks were prepared. Histopathological examination was performed after the sections had been stained with hematoxylin-eosin. Tumor necrosis factor alpha and caspase-3 antibodies were used on immunohistochemical analysis. In the esophageal burn group, necrosis, degeneration and numerous apoptotic cells, as well as intense inflammatory cell infiltration and fibrosis in the muscle layer were observed under light microscope. In the treated group, remodeling of epithelial cells with marked reduction in the connective tissue collagen content was observed, as well as marked reduction in the volume of collagen and abundance of inflammatory cells in blood vessels. Gallic acid treatment may help heal esophageal burns and prevent complications.

Dual actions of gallic acid and andrographolide trigger AdipoR1 to stimulate insulin secretion in a streptozotocin-induced diabetes rat model.

Common treatments for the management of diabetes have limitations due to side effects, hence the need for continuous research to discover new remedies with better therapeutic efficacy. Previously, we have reported that the combination treatment of gallic acid (20mg/kg) and andrographolide (10mg/kg) for 15 days demonstrated synergistic hypoglycemic activity in the streptozotocin (STZ)-induced insulin-deficient diabetes rat model. Here, we attempt to further elucidate the effect of this combination therapy at the biochemical, histological and molecular levels. Our biochemical analyses showed that the combination treatment significantly increased the serum insulin level and decreased the total cholesterol and triglyceride level of the diabetic animals. Histological examinations of H&E stained pancreas, liver, kidney and adipose tissues of combination-treated diabetic animals showed restoration to the normalcy of the tissues. Besides, the combination treatment significantly enhanced the level of glucose transporter-4 (GLUT4) protein expression in the skeletal muscle of treated diabetic animals compared to single compound treated and untreated diabetic animals. The molecular docking analysis on the interaction of gallic acid and/or andrographolide with the adiponectin receptor 1 (AdipoR1), a key component in the regulation of pancreatic insulin secretion, revealed a greater binding affinity of AdipoR1 to both compounds compared to individual compounds. Taken together, these findings suggest the combination of gallic acid and andrographolide as a potent therapy for the management of diabetes mellitus.

Protective effect of gallic acid against thioacetamide-induced metabolic dysfunction of lipids in hepatic and renal toxicity

BackgroundGallic acid (GA) has significant antioxidant bioactivity and can prevent diet-induced hypertriglyceridemia by reducing adipocytes. GA was also observed to enhance cell glucose uptake. MethodsThe current study looked at the effect of gallic acid (GA) (100 mg, 200 mg/kg orally) on liver and kidney damage caused by thioacetamide (TAA; 100 mg/Kg via intraperitoneal route). TAA was treated thrice weekly for eight weeks, whereas gallic acid was administered daily. ResultsGA alleviated the thioacetamide-induced decreases in hepatic or renal reduced glutathione (GSH) or increases in malondialdehyde (MDA, an indication of lipid peroxidation). TAA treatment significantly increased plasma inflammatory markers, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP), liver enzymes, Gamma-glutamyltransferase (GGT), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and kidney function parameters (creatinine and urea) and uric acid. However, these values decreased after GA treatment in a dose-dependent manner. Furthermore, GA mitigated the considerable decrease in plasma protein caused by TAA. GA also reduced hepatic fibrosis or histological abnormalities in the liver and kidney. ConclusionOur results suggest that GA may attenuate TAA-induced liver and kidney toxicity via suppression of oxidative stress and inflammatory markers. Moreover, the hypolipidemic effect of GA may be considered another route for protection.

Gallic acid inhibits neuroinflammation and reduces neonatal hypoxic-ischemic brain damages.

Neuroinflammation is a leading cause of secondary neuronal injury in neonatal hypoxic-ischemic encephalopathy (HIE). Regulation of neuroinflammation may be beneficial for treatment of HIE and its secondary complications. Gallic acid (GA) has been shown to have anti-inflammatory and antioxidant effects. In this report we found that oxygen-glucose deprivation and/reoxygenation (OGD/R)-induced cell death, and the generation of excessive reactive oxygen species (ROS) and inflammatory cytokines by microglia were inhibited by GA treatment. Furthermore, GA treatment reduced neuroinflammation and neuronal loss, and alleviated motor and cognitive impairments in rats with hypoxic-ischemic brain damage (HIBD). Together, our results reveal that GA is an effective regulator of neuroinflammation and has potential as a pharmaceutical intervention for HIE therapy.

Gallic acid impairs fructose-driven de novo lipogenesis and ameliorates hepatic steatosis via AMPK-dependent suppression of SREBP-1/ACC/FASN cascade

Accumulating evidence suggests that de novo lipogenesis is a typical characteristic facilitating nonalcoholic fatty liver disease (NAFLD) progression. Gallic acid (GA) is a naturally occurring phenolic acid with metabolic disease-related clinical significance and preclinical benefits. This study aimed to evaluate the anti-steatotic potentials of GA in a fructose-induced NAFLD mouse model featuring a hepatic lipogenic phenotype. The results revealed that GA alleviated hepatic steatosis, oxidative stress, and inflammatory response in fructose-fed mice. Mechanistically, GA treatment restored AMP-activated protein kinase α (AMPKα) phosphorylation, resulting in downregulations of pro-lipogenic factors, including sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FASN), and acetyl-CoA carboxylase (ACC), in hepatocytes of mice and in vitro. Furthermore, computational docking analysis indicated that GA could directly interact with AMPKα/β subunits to stabilize its activation. These results suggest that GA ameliorates fructose-induced hepatosteatosis by restraining hepatic lipogenesis via AMPK-dependent suppression of the SREBP-1/ACC/FASN cascade. Altogether, this study demonstrates that GA supplement may be a promising therapeutic strategy in NAFLD, especially in the subset with enhanced hepatic lipogenesis.

Gallic acid suppresses the progression of triple-negative breast cancer HCC1806 cells via modulating PI3K/AKT/EGFR and MAPK signaling pathways.

Triple-negative breast cancer (TNBC) is a severe threat to women's health because of its aggressive nature, early age of onset, and high recurrence rate. Therefore, in this study, we aimed to evaluate the anti-tumor effects of Gallic acid (GA) on the TNBC HCC1806 cells in vitro. The cell proliferation was detected by MTT and plate clone formation assays, cell apoptosis, cell cycle, and mitochondrial membrane potential (MMP) were analyzed by flow cytometry and Hoechst 33258 staining assays, and the intracellular reactive oxygen species (ROS) accumulation were also investigated. Real-Time PCR and western blot were examined to explore the mechanism of action. The results indicated that GA suppressed HCC1806 cells proliferation and promoted HCC1806 cells apoptosis. Meanwhile, GA treatment changed the morphology of the HCC1806 cells. In addition, GA blocked the HCC1806 cells cycle in the S phase, and it induced cells apoptosis accompanied by ROS accumulation and MMP depolarization. Real-Time PCR results suggested that GA increased Bax, Caspase-3, Caspase-9, P53, JINK and P38 mRNA expression, and decreased Bcl-2, PI3K, AKT and EGFR mRNA expression. Western blotting results suggested that GA increased Bax, cleaved-Caspase-3, cleaved-Caspase-9, P53, P-ERK1/2, P-JNK, P-P38 proteins expression, and decreased Bcl-2, P-PI3K, P-AKT, P-EGFR proteins expression. Furthermore, molecular docking suggested that GA has the high affinity for PI3K, AKT, EGFR, ERK1/2, JNK, and P38. In conclusion, GA could suppress HCC1806 cells proliferation and promote HCC1806 cells apoptosis through the mitochondrial apoptosis pathway and induces ROS generation which further inhibits PI3K/AKT/EGFR and activates MAPK signaling pathways. Our study will provide some new references for using GA in the treatment of TNBC.

Apoptosis Event in Hela Cells Treated with Cisplatin, Gallic Acid and Combination of Both

Adverse effect of conventional chemotherapeutic agent using single anticancer drugs had led to application of combination therapy in cancer treatments. Combination of polyphenolic compounds and anticancer agent was studied and shown promising outcomes in vitro. In cancer treatment, mode of cell death through apoptosis is one of the targeted approaches in many preclinical drug development studies and has been identified as a key mechanism of chemotherapy-induced cell death. 
 
 Hence, this study was conducted to evaluate the apoptosis event of HeLa cells treated with gallic acid (GA) combined with cisplatin (CIS). HeLa cells were treated for 24,48 and 72 hours with CIS and GA at IC50 (Table 1) concentrations, and the combination of CIS and GA (CIS– GA) was chosen based on a previous study (66.73 percent cell inhibition [1]. To compare the anticancer effects of cisplatin and gallic acid individually and in-combination on apoptosis in HeLa cells, flow cytometry assay was carried out. 
 According to the findings, during every incubation period, the CIS-GA combination treatment group consistently showed the highest level of antiproliferative activity in HeLa cells, followed by the CIS and GA treatment group. CIS and GA combined treatment response was time-dependent, with an increase in apoptotic cells as incubation time increase (Figure 1). At 72 hours, the combination of CIS and GA treatment showed a significant improvement (74.6%), and improvements were also shown after 24 and 48 hours (56 percent and 60.2 percent).
 Taken together, these findings suggest that combination therapy enhances the cell death magnitude in HeLa cells. Additionally, these findings have positive implications for the use of a combination therapy approach in cancer treatment.

The molecular evaluation of thioredoxin (TXN1 & TXN2), thioredoxin reductase 1 (TXNRd1), and oxidative stress markers in a binary rat model of hypo- and hyperthyroidism after treatment with gallic acid

Oxidative stress plays an important role in the pathology of thyroid disorders. This study examined the effect of gallic acid (GA) on the oxidative status and expression of liver antioxidant genes including thioredoxin (TXN1 & TXN2) and thioredoxin reductase1 (TXNRd1) in hypo- and hyperthyroid rat models. Forty-nine male Wistar rats were randomly assigned into seven groups as follows: control group, hypothyroid and hyperthyroid groups respectively induced by propylthiouracil and levothyroxine, hypo- and hyper thyroid-treated groups (where the groups were separately treated with 50 and 100 mg/kg of GA daily, orally). The levels of thyroid hormones and serum oxidative stress markers were evaluated after 5 weeks. The relative expression of TXN1,2 and TXNRd1 genes was measured via real-time qRT-PCR. The mean level of total antioxidant capacity (TAC), malondialdehyde, and uric acid index diminished in the hypothyroid group. Increased TAC reached almost the level of control in hypothyroid groups treated with GA. Elevation of thiol index in the hypothyroid group was observed (p < 0.01), which diminished to the control level after GA treatment. The relative expression of TXN1, TXNRd1, and TXN2 genes in the hypothyroid and hyperthyroid groups significantly increased compared to the control group (p ≥ 0.05), but in the groups treated with GA, the expression of these genes declined significantly (p ≥ 0.05). Our results indicated GA can affect the expression of TXN system genes in the rat liver. Also, the results suggest GA has a more positive effect on modulating serum oxidative parameters in hypothyroid rat models than in hyperthyroid.

Gallic acid and heat moisture treatment improve pasting, rheological, and microstructure properties of Chinese yam starch-chitosan gels: A comparative study

Nowadays，It is difficult for the polysaccharide-starch system to meet demand of practical production owing to the poor gel properties. Therefore, aiming to further improve the practical application of polysaccharide-starch gel, the effects of gallic acid (GA) and heat moisture treatment (HMT) on the gel properties and microstructure of yam starch/chitosan (YS/CS) composite gels were investigated. Swell power (SP) results showed that GA and HMT treatment respectively reduced the SP of YS gel by 3.24 g/g and 6.03 g/g, given that GA and HMT decrease the rheology of the water phase inhibiting the entry of water into the swollen starch. In the pasting process, HMT reduced pasting viscosity of the HMT/YS system because only little amylose was leached in the medium for elevating its viscosity after HMT. The rheological properties suggested that high temperature treatment of HMT facilitated the disruption and disintegration of starch granules resulting dynamic modulus had a decline trend. The elastic properties of GA/YS gels were enhanced with the addition of GA, which could be supported by the thicken lamellar observed in its microstructure. In general, GA and HMT effectively alter the gel properties of YS/CS gel system, and facilitate its practical application in food industry.

Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor

Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1β, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1β and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.

Evaluation of gallic acid on membrane damage of Yersinia enterocolitica and its application as a food preservative in pork

This study was aimed to examine the membrane damage mechanism of gallic acid (GA) on Yersinia enterocolitica BNCC 108930, and to explore whether GA can prolong the shelf life of pork. The minimal inhibitory concentration (MIC) of GA against Y. enterocolitica was determined by adopting the broth microdilution method. Second, an investigation was conducted on the morphological and physiological variations of Y. enterocolitica after the GA treatment. Finally, a response surface approach was used to establish the growth inhibition model of GA against Y. enterocolitica in pork. The MIC of GA against Yersinia enterocolitica BNCC 108930 was 2.5 mg/mL. GA affects the membrane integrity of Y. enterocolitica, as demonstrated by a significant decrease in intracellular ATP and pH. The results showed that the number of Y. enterocolitica in pork meat containing 5 mg/g of GA decreased by 2 logarithmic cycles during storage at 4 °C for 3 days. According to the obtained findings, GA could be used as a food preservative to prolong the shelf life of pork.

Synergistic effects of ε-polylysine hydrochloride and gallic acid on Shewanella putrefaciens and quality of refrigerated sea bass fillets

The abundant nutrients of raw sea bass are excellent media for specific microorganisms like Shewanella putrefaciens, which cause fish spoilage. In this study, gallic acid (GA), protocatechuic acid (PA) and chlorogenic acid (CA) were tested for their synergistic antibacterial effects with ε-polylysine hydrochloride (PL). A strong synergistic inhibitory effect against S. putrefaciens was observed in PL and GA treatment. The combination of 1/8 MIC PL and 1/4 MIC GA completely inhibited S. putrefaciens growth and caused cell death. This combination significantly damaged the cell structure, and induced serious leakage of electrolytes, nucleic acid, and protein. GA, PL and PL-GA treatments significantly reduced sensory deterioration, total viable counts, total volatile base nitrogen and thiobarbituric acid value of sea bass fillets during 4 °C storages, with PL-GA showing the best effect. The results suggested that the combination of PL and GA might be an effective preservative to control marine fish spoilage.

Gallic Acid Inhibits Mesaconitine-Activated TRPV1-Channel-Induced Cardiotoxicity.

Aconiti Kusnezoffii Radix (Caowu) is often combined or processed with Chebulae Fructus (Hezi) to achieve attenuation purposes in Mongolian medicine. Mesaconitine (MA), a main bioactive ingredient of Caowu, is also famous for its high cardiotoxicity while exerting good anti-inflammatory and analgesic properties. Gallic acid (GA), one of the leading chemical components in Hezi, possesses cardiac protection. This study aimed to clarify the detoxification effects of GA from Hezi on MA-induced cardiotoxicity and whether the detoxification mechanism is related to the TRPV1 channel. Cell viability was determined by methyl thiazol tetrazolium (MTT), and lactate dehydrogenase (LDH) leakage rate was determined by ELISA. Hoechst 33258, JC-1, DCFH-DA, and Fluo-3 AM staining were conducted to detect apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS), and Ca2+ respectively; TRPV1 channel current was recorded by whole-cell patch-clamp technology to observe the effect of GA and MA alone or in combination on TRPV1 channel. The results showed that GA exhibited pronounced detoxification effects on MA-induced cardiotoxicity. GA significantly inhibited the MA-induced decrease in cell viability; suppressed the MA-induced LDH leakage rate, apoptosis, and the release of ROS and Ca2+; and alleviated the reduction of mitochondrial membrane potential. We found that MA-induced cardiotoxicity was significantly attenuated in H9c2 cells pretreated with the TRPV1 antagonist BCTC. In the whole-cell patch-clamp experiment, the TRPV1 channel current increase was caused by the GA and MA treatment, whereas it was reduced by the cotreatment of GA and MA. Our data demonstrate that GA in Hezi can reduce MA-induced cardiotoxicity by inhibiting intracellular Ca2+ influx, restoring mitochondrial membrane potential, and reducing apoptosis. The detoxification mechanism may be related to the desensitization of the TRPV1 channel by the combined application of MA and GA.

Gallic acid attenuates cerebral ischemia/re-perfusion-induced blood–brain barrier injury by modifying polarization of microglia

Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time.

Exogenous Application of Gallic Acid Induces the Direct Defense of Tea Plant Against Ectropis obliqua Caterpillars.

Gallic acid (GA), an important polyphenolic compound in the plant, is a well-known antioxidant, antihyperglycemic, and anti-lipid peroxidative agent. Recently, GA treatment exhibited ameliorative effects on plants in response to some abiotic stresses. However, the elicitation effect of GA on plant defense against herbivorous insects has not yet been reported. In this study, we found that the exogenous application of GA induced the direct defense of tea plant (Camellia sinensis) against tea geometrid (Ectropis obliqua) larvae, through activating jasmonic acid (JA) signaling and phenylpropanoid pathways. These signaling cascades resulted in the efficient induction of several defensive compounds. Among them, astragalin, naringenin, and epigallocatechin-3-gallate were the three of the most active anti-feeding compounds. However, the exogenous GA treatment did not affect the preference of E. obliqua female moths and larval parasitoid Apanteles sp. Our study suggests that GA may serve as an elicitor that triggers a direct defense response against tea geometrid larvae in tea plants. This study will help to deepen the understanding of the interaction between plants and phytophagous insects and also provide theoretical and technical guidance for the development of plant defense elicitors.

Gallic Acid as a Non-Selective Inhibitor of α/β-Hydrolase Fold Enzymes Involved in the Inflammatory Process: The Two Sides of the Same Coin.

(1) Background: Gallic acid (GA) has been characterized as an effective anti-inflammatory, antivenom, and promising drug for therapeutic use. (2/3) Methods and Results: GA was identified from ethanolic extract of fresh pitanga (Eugenia uniflora) leaves, which was identified using commercial GA. Commercial GA neutralized the enzymatic activity of secretory PLA2 (sPLA2) by inhibiting the active site and inducing changes in the secondary structure of the enzyme. Pharmacological edema assays showed that GA strongly decreased edema when the compound was previously incubated with sPLA2. However, prior treatment of GA (30 min before) significantly increased the edema and myotoxicity induced by sPLA2. The molecular docking results of GA with platelet-acetylhydrolase (PAF-AH) and acetylcholinesterase reveal that this compound was able to interact with the active site of both molecules, inhibiting the hydrolysis of platelet-activating factor (PAF) and acetylcholine (ACh). (4) Conclusion: GA has a great potential application; however, our results show that this compound can also induce adverse effects in previously treated animals. Additionally, the increased edema and myotoxicity observed experimentally in GA-treated animals may be due to the inhibition of PAF-AH and Acetylcholinesterase.

Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression

Research questionWomen are increasingly suffering from polycystic ovary syndrome (PCOS). Its pathophysiology is still unknown, though. The purpose of this study was to ascertain how gallic acid affected the pathophysiology of the ovary in an animal model of polycystic ovary syndrome. We also showed the potential mechanism of adiponectin involvement in endocrine metabolic changes in PCOS mice and the function of adiponectin, which appear to be frequent factors in PCOS. DesignEighteen adult female Parkes strain mice (Age: 4–5 weeks) having body weight of 16–21 g were separated into three groups at random with 6 animals in each group as follows: Group I serving the control, received water and normal diet for 81 days; group II received oral gavage administration of letrozole (LETZ)(6 mg/kg b.w.daily), which was dissolved in 0.9 % NaCl solution for 21 days for the induction of PCOS and left untreated for 60 days; Group III received oral gavage administration of LETZ (6 mg/kg) for first 21 days followed by the administration of gallic acid (GA) (75 mg/kg b.w. orally daily) for 60 days. ResultsWe found LETZ-treated mice experienced PCOS-like symptoms, including increased Serum testosterone, LH/FSH ratio, body and ovarian weight, blood glucose, serum insulin levels and inflammatory Cytokines. We also found decreased serum estrogen, oxidant capacity and enzyme activity and altered ovarian cytoarchitecture, with multiple cysts apart from irregular estrous cycle. Furthermore, mRNA expression levels CYP11a, CYP19a1, Kitl, PTGS2 and Adipo R1 were decreased. Furthermore, LETZ-induced PCOS mice when treated with GA we observed decrease in testosterone, LH, LH/FSH ratio, blood glucose, serum insulin and inflammatory cytokines. GA treatment in PCOS mice also increased estrogen levels, and oxidant capacity as well as enzyme activity. Furthermore mRNA expression levels of CYP11a1, CYP19a1, KITL, PTGS2 and Adipo R1 were also increased in LETZ+GA treated mice. These changes were linked to lower levels of circulating adiponectin and were altered when the mice were administered with gallic acid. ConclusionGallic acid might be a potential therapy in treating PCOS by regulating endocrine and metabolic abnormalities that are brought on by a drop in adiponectin levels along with hyperandrogenism. Additionally, adiponectin seems to be a frequent factor in PCOS. In addition to reducing inflammation-related comorbidities linked to LETZ-induced PCOS, GA enhances mRNA expression levels CYP11a, CYP19a1, Kitl and PTGS2 and hence reduces endocrine and metabolic abnormalities.

Synergistically enhanced Salmonella Typhimurium reduction by sequential treatment of organic acids and atmospheric cold plasma and the mechanism study

Salmonella, a foodborne pathogen, has been frequently associated with recalls of fresh food products, including poultry meat products. Atmospheric cold plasma (ACP) is a novel non-thermal technology, which has potential to reduce pathogens in food products. This study demonstrates the synergistic interactions of food grade organic acids (i.e., lactic acid (LA) or gallic acid (GA)) and ACP to inactivate Salmonella enterica Typhimurium ATCC 13311 inoculated on polycarbonate membrane filter paper and poultry meat surface. Organic acids were used in the form of a spray to enhance dispersion on samples surface. The sequential treatment of organic acid followed by ACP synergistically reduced S. Typhimurium on poultry meat surface. Irrespective of the type of organic acid, an average reduction of more than 3.5 log CFU/cm2 in S. Typhimurium on filter paper was obtained, when a combination of 10 mM LA or GA with an ACP exposure of 30 s was tested. However, the individual treatments of LA, GA, and ACP resulted in only 0.4, 0.3, 1.2 log CFU/cm2 reduction in S. Typhimurium, respectively. On poultry meat surface, a higher level of organic acid concentration (i.e., 50 mM) in combination with 30 s ACP was required to achieve more than 2.5 log CFU/cm2 reduction in S. Typhimurium. Our investigation on inactivation mechanisms revealed that the sequential treatment of LA or GA with ACP resulted in a significantly higher level of membrane permeability and membrane lipid peroxidation in S. Typhimurium cells. Additionally, the combined treatment significantly reduced the cell metabolic activity and affected the intracellular reactive oxygen species level of S. Typhimurium. In summary, this study demonstrated the potential synergistic benefits of combining organic acids and ACP to achieve a higher level of bacterial inactivation.