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Reducing nitrites tends to increase the accumulation of hazardous biogenic amines (BAs) in Chinese fermented sausages (CFSs). Gallic acid (GA) has emerged as a potential alternative to reduce nitrite usage and control BAs. This study explored how GA inhibits BAs and nitrosamines accumulation in reduced-nitrite CFSs. Results demonstrated that combining 0.05% (w/w) GA with reduced nitrite effectively curbed BAs and N-nitrosodimethylamine, decreasing total BA from 271.48 to 125.46 mg/kg. Fifty-one metabolites associated with the metabolism of BAs and N-nitrosodimethylamine were identified. GA boosted Lactococcus while reducing spoilage bacteria and Macrococcus. This dual regulation suppressed BAs and dimethylamine accumulation by regulating amino acids and trimethylamine pathways. Consequently, GA achieved an 89.86% reduction in N-nitrosodimethylamine by decreasing the key precursors like putrescine, dimethylamine, and nitrite. These findings offer new insights into utilizing GA and similar plant polyphenols to manage BAs and nitrosamines in meat products with reduced nitrite usage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Paraben hydrolase and tannase catalyze the hydrolysis of parabens (4-hydroxybenzoic acid esters) and gallic acid (3,4,5-trihydroxybenzoic acid) esters, respectively. Paraben hydrolase (AoPrbA) and tannase (AoTanB) from Aspergillus oryzae belong to the tannase family in the ESTHER database. However, the substrate specificities of AoPrbA and AoTanB are narrow. Based on structural information of Aspergillus niger tannase (PDB code 7k4o), we constructed five single variants of AoPrbA (Thr200Glu, Phe231Gln, Leu232Gln, Ile361Tyr, and Leu428Ser) and four of AoTanB (Glu203Asp, Glu203Thr, His237Ala, and Ser440Leu) to investigate substrate discrimination between AoPrbA and AoTanB. Each variant was expressed in Pichia pastoris and were purified from the culture supernatant. Five purified variants of AoPrbA and four variants of AoTanB showed reduced paraben hydrolase and tannase activities compared with AoPrbA and AoTanB wild types, respectively. Interestingly, the AoPrbA wild type did not hydrolyze gallic acid methyl ester, whereas the Thr200Glu, Leu232Gln, and Leu428Ser variants did, indicating that these three variants acquired tannase activity. In particular, the Leu428Ser variant exhibited considerably greater hydrolysis of gallic acid and protocatechuic acid methyl esters. Meanwhile, the AoTanB wild type, and Glu203Asp, His237Ala and Ser440Leu variants hydrolyzed the protocatechuate methyl and 4-hydroxybenzoate ethyl esters; however, the Glu203Thr variant did not hydrolyze above-mentioned substrates. Additionally, the ratio of paraben hydrolase activity to tannase activity in Ser440Leu was markedly elevated., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives., (© 2024 Wiley Periodicals LLC.)

Background: Caenorhabditis elegans (C. elegans) has been recognized for being a useful model organism in small-molecule drug screens and drug efficacy investigation. However, there remain bottlenecks in evaluating such processes as drug uptake and distribution due to a lack of appropriate chemical tools., Purpose: This study aims to prepare fluorescence-labeled leonurine as an example to monitor drug uptake and distribution of small molecule in C. elegans and living cells., Methods: FITC-conjugated leonurine (leonurine-P) was synthesized and characterized by LC/MS, NMR, UV absorption and fluorescence intensity. Leonurine-P was used to stain C. elegans and various mammalian cell lines. Different concentrations of leonurine were tested in conjunction with a competing parent molecule to determine whether leonurine-P and leonurine shared the same biological targets. Drug distribution was analyzed by imaging. Fluorometry in microplates and flow cytometry were performed for quantitative measurements of drug uptake., Results: The UV absorption peak of leonurine-P was 490∼495 nm and emission peak was 520 nm. Leonurine-P specifically bound to endogenous protein targets in C. elegans and mammalian cells, which was competitively blocked by leonurine. The highest enrichment levels of leonurine-P were observed around 72 h following exposure in C. elegans. Leonurine-P can be used in a variety of cells to observe drug distribution dynamics. Flow cytometry of stained cells can be facilely carried out to quantitatively detect probe signals., Conclusions: The strategy of fluorescein-labeled drugs reported herein allows quantification of drug enrichment and visualization of drug distribution, thus illustrates a convenient approach to study phytodrugs in pharmacological contexts., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Salinity stress significantly impacts crops, disrupting their water balance and nutrient uptake, reducing growth, yield, and overall plant health. High salinity in soil can adversely affect plants by disrupting their water balance. Excessive salt levels can lead to dehydration, hinder nutrient absorption, and damage plant cells, ultimately impairing growth and reducing crop yields. Gallic acid (GA) and zinc ferrite (ZnFNP) can effectively overcome this problem. GA can promote root growth, boost photosynthesis, and help plants absorb nutrients efficiently. However, their combined application as an amendment against drought still needs scientific justification. Zinc ferrite nanoparticles possess many beneficial properties for soil remediation and medical applications. That's why the current study used a combination of GA and ZnFNP as amendments to wheat. There were 4 treatments, i.e., 0, 10 µM GA, 15 μM GA, and 20 µM GA, without and with 5 μM ZnFNP applied in 4 replications following a completely randomized design. Results exhibited that 20 µM GA + 5 μM ZnFNP caused significant improvement in wheat shoot length (28.62%), shoot fresh weight (16.52%), shoot dry weight (11.38%), root length (3.64%), root fresh weight (14.72%), and root dry weight (9.71%) in contrast to the control. Significant enrichment in wheat chlorophyll a (19.76%), chlorophyll b (25.16%), total chlorophyll (21.35%), photosynthetic rate (12.72%), transpiration rate (10.09%), and stomatal conductance (15.25%) over the control validate the potential of 20 µM GA + 5 μM ZnFNP. Furthermore, improvement in N, P, and K concentration in grain and shoot verified the effective functioning of 20 µM GA + 5 μM ZnFNP compared to control. In conclusion, 20 µM GA + 5 μM ZnFNP can potentially improve the growth, chlorophyll contents and gas exchange attributes of wheat cultivated in salinity stress. More investigations are suggested to declare 20 µM GA + 5 μM ZnFNP as the best amendment for alleviating salinity stress in different cereal crops., (© 2024. The Author(s).)

Background: Syringic acid (SA) is a high-value natural compound with diverse biological activities and wide applications, commonly found in fruits, vegetables, and herbs. SA is primarily produced through chemical synthesis, nonetheless, these chemical methods have many drawbacks, such as considerable equipment requirements, harsh reaction conditions, expensive catalysts, and numerous by-products. Therefore, in this study, a novel biotransformation route for SA production was designed and developed by using engineered whole cells., Results: An O-methyltransferase from Desulfuromonas acetoxidans (DesAOMT), which preferentially catalyzes a methyl transfer reaction on the meta-hydroxyl group of catechol analogues, was identified. The whole cells expressing DesAOMT can transform gallic acid (GA) into SA when S-adenosyl methionine (SAM) is used as a methyl donor. We constructed a multi-enzyme cascade reaction in Escherichia coli, containing an endogenous shikimate kinase (AroL) and a chorismate lyase (UbiC), along with a p-hydroxybenzoate hydroxylase mutant (PobA ** ) from Pseudomonas fluorescens, and DesAOMT; SA was biosynthesized from shikimic acid (SHA) by using whole cells catalysis. The metabolic system of chassis cells also affected the efficiency of SA biosynthesis, blocking the chorismate metabolism pathway improved SA production. When the supply of the cofactor NADPH was optimized, the titer of SA reached 133 μM (26.2 mg/L)., Conclusion: Overall, we designed a multi-enzyme cascade in E. coli for SA biosynthesis by using resting or growing whole cells. This work identified an O-methyltransferase (DesAOMT), which can catalyze the methylation of GA to produce SA. The multi-enzyme cascade containing four enzymes expressed in an engineered E. coli for synthesizing of SA from SHA. The metabolic system of the strain and biotransformation conditions influenced catalytic efficiency. This study provides a new green route for SA biosynthesis., (© 2024. The Author(s).)

Plant-derived phenolic gallic acid (GA) is an important raw material for antioxidants and food additives. Efforts to ferment GA using microbial processes have aimed at minimizing production costs and environmental load using enzymes that hydroxylate p-hydroxybenzoate and protocatechuate (PCA). Here, we found a p-hydroxybenzoate hydroxylase (PobA) in the bacterium Hylemonella gracilis NS1 (HgPobA) with 1.5-fold more hydroxylation activity than that from Pseudomonas aeruginosa PAO1 and thus converted PCA to GA more efficiently. The PCA hydroxylation activity of HgPobA was improved by introducing the amino acid substitutions L207V/Y393F or T302A/Y393F. These mutants had 2.9- and 3.7-fold lower K m app for PCA than wild-type HgPobA. An Escherichia coli strain that reinforces shikimate pathway metabolism and produces HgPobA when cultured for 60 h generated 0.27 g L -1 of GA. This is the first report of fermenting glucose to generate GA using a natural enzyme from the PobA family. The E. coli strain harboring the HgPobA L207V/Y393F mutant increased GA production to 0.56 g L -1 . During the early stages of culture, GA was fermented at a 10-fold higher rate by a strain producing either HgPobA L207V/Y393F or T302A/Y393F compared with wild-type HgPobA, which agreed with the high k cat app /K m app PCA values of this mutant. We enhanced a PobA isozyme and its PCA hydroxylating function to efficiently and cost-effectively ferment GA.

Bergenin, a rare C-glycoside of 4-O-methyl gallic acid with pharmacological properties of antitussive and expectorant, is widely used in clinics to treat chronic tracheitis in China. However, its low abundance in nature and structural specificity hampers the accessibility through traditional crop-based manufacturing or chemical synthesis. In the present work, we elucidate the biosynthetic pathway of bergenin in Ardisia japonica by identifying the highly regio- and/or stereoselective 2-C-glycosyltransferases and 4-O-methyltransferases. Then, in Escherichia coli, we reconstruct the de novo biosynthetic pathway of 4-O-methyl gallic acid 2-C-β-D-glycoside, which is the direct precursor of bergenin and is conveniently esterified into bergenin by in situ acid treatment. Moreover, further metabolic engineering improves the production of bergenin to 1.41 g L -1 in a 3-L bioreactor. Our work provides a foundation for sustainable supply of bergenin and alleviates its resource shortage via a synthetic biology approach., (© 2024. The Author(s).)

This study aimed to investigate the role of amylose and amylopectin in the formation of starch-polyphenol complex and elucidate the interaction mechanisms. Gallic acid (GA) was used to complex with maize starch with various amylose contents. Results showed GA formed V-type crystals with normal maize starch (NMS) and high amylose maize starch (HAMS), while higher relative crystallinity was exhibited in HAMS-GA complexes than NMS counterparts. Molecular structure analysis revealed more amylose in GA-starch complexes than in treated starch counterparts without GA, and this was more apparent in HAMS than NMS, implying amylose is preferred to complex with GA than amylopectin. FTIR detected higher R 1047/1022 value in starch-GA complexes than their starch counterparts without GA, suggesting increased short-range ordered structrure of complexes. Typical signatures of hydrophobic interactions were further revealed by isothermal titration calorimetry, indicating the complexation of GA to starch is mainly through hydrophobic bonds. More binding sites were observed for HAMS (72.50) than NMS (11.33), which proves the preferences of amylose to bind with GA. Molecular dynamics simulated the complexation of GA to amylose, and confirmed hydrophobic bond is the main interaction force. These findings would provide guidance for precise design and utilization of starch-polyphenol complexes in functional foods., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gallic acid (GA), a dietary phenolic acid with potent antioxidant activity, is widely distributed in edible plants. GA has been applied in the food industry as an antimicrobial agent, food fresh-keeping agent, oil stabilizer, active food wrap material, and food processing stabilizer. GA is a potential dietary supplement due to its health benefits on various functional disorders associated with oxidative stress, including renal, neurological, hepatic, pulmonary, reproductive, and cardiovascular diseases. GA is rapidly absorbed and metabolized after oral administration, resulting in low bioavailability, which is susceptible to various factors, such as intestinal microbiota, transporters, and metabolism of galloyl derivatives. GA exhibits a tendency to distribute primarily to the kidney, liver, heart, and brain. A total of 37 metabolites of GA has been identified, and decarboxylation and dihydroxylation in phase I metabolism and sulfation, glucuronidation, and methylation in phase Ⅱ metabolism are considered the main in vivo biotransformation pathways of GA. Different types of nanocarriers, such as polymeric nanoparticles, dendrimers, and nanodots, have been successfully developed to enhance the health-promoting function of GA by increasing bioavailability. GA may induce drug interactions with conventional drugs, such as hydroxyurea, linagliptin, and diltiazem, due to its inhibitory effects on metabolic enzymes, including cytochrome P450 3A4 and 2D6, and transporters, including P-glycoprotein, breast cancer resistance protein, and organic anion-transporting polypeptide 1B3. In conclusion, in-depth studies of GA on food industry applications, health benefits, bioavailability, nano-delivery systems, and drug interactions have laid the foundation for its comprehensive application as a food additive and dietary supplement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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

Background and Objective: Gallic acid (GA) possesses various beneficial functions including antioxidant, anticancer, anti-inflammatory as well as inhibiting osteoclastogeneis. However, effects on osteogenic differentiation, especially in human ligament periodontal (hPDL) cells, remain unclear. Thus, the aim of this study was to evaluate the function of GA on osteogenesis and anti-inflammation in hPDL cells and to explore the involved underlying mechanism., Methods: Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) treatment was used as a model for periodontitis. ROS production was determined by H2DCFDA staining. Trans-well and wound healing assays were performed for checking the migration effect of GA. Alizarin red and alkaline phosphatase activity (ALP) assays were performed to evaluate osteogenic differentiation. Osteogenesis and inflammatory-related genes and proteins were measured by real-time PCR and western blot., Results: Our results showed that GA-treated hPDL cells had higher proliferation and migration effect. GA inhibited ROS production-induced by Pg-LPS. Besides, GA abolished Pg-LPS-induced inflammation cytokines (il-6, il-1β) and inflammasome targets (Caspase-1, NLRP3). In addition, GA promoted ALP activity and mineralization in hPDL cells, lead to enhance osteoblast differentiation process. The effect of GA is related to G-protein-coupled receptor 35 (GPR35)/GSK3β/β-catenin signaling pathway., Conclusion: GA attenuated Pg-LPS-induced inflammatory responses and periodontitis in hPDL cells. Taken together, GA may be targeted for therapeutic interventions in periodontal diseases., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti-inflammatory, and anti-microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP-induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N-acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor-α, interleukin-1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5-trihydroxybenzoic acid region. These effects of EG against APAP-induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti-inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication., (© 2023 John Wiley & Sons Ltd.)

In this study, the structure, function, and digestibility of noncovalent complexes and covalent conjugates formed by acid-soluble collagen with polyphenols of different structures (quercetin, epicatechin, gallic acid, chlorogenic acid, procyanidin, and tannic acid) were investigated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that polyphenols were covalently bound to collagen by laccase catalytic oxidation. Biolayer interferometry revealed that the noncovalent binding strength of polyphenols to collagen from high to low was quercetin > gallic acid > chlorogenic acid > epicatechin, which was consistent with the trend of covalent polyphenol binding. Procyanidin and tannic acid had strong noncovalent binding, but their covalent binding ability was weak. Compared with the pure collagen, the complexes improved emulsification and antioxidant properties (more than 2.5 times), and the conjugates exhibited better thermal stability (99.4-106.8 °C) and antidigestion ability (reduced by more than 37%). The finding sheds new light on the use of collagen as a functional food ingredient in the food industry.

Aluminum toxicity is the main factor limiting the elongation of plant roots in acidic soil. The tree species Eucalyptus camaldulensis is considerably more resistant to aluminum than herbaceous model plants and crops. Hydrolyzable tannins (HTs) accumulating in E. camaldulensis roots can bind and detoxify the aluminum taken up by the roots. However, in herbaceous model plants, HTs do not accumulate and the genes involved in the HT biosynthetic pathway are largely unknown. The aim of this study was to establish a method for reconstituting the HT biosynthetic pathway in the HT non-accumulating model plant Nicotiana benthamiana. Four E. camaldulensis enzymes were transiently expressed in N. benthamiana leaves via Agrobacterium tumefaciens-mediated transformation. These enzymes included dehydroquinate dehydratase/shikimate dehydrogenases (EcDQD/SDH2 and EcDQD/SDH3), which catalyze the synthesis of gallic acid, the first intermediate of the HT biosynthetic pathway that branches off from the shikimate pathway. The others were UDP-glycosyltransferases (UGT84A25 and UGT84A26), which catalyze the conversion of gallic acid to β-glucogallin, the second intermediate. The co-expression of the EcDQD/SDHs in transgenic N. benthamiana leaf regions promoted the synthesis of gallic acid. Moreover, the co-expression of the UGT84As in addition to the EcDQD/SDHs resulted in the biosynthesis of β-glucogallin, the universal metabolic precursor of HTs. Thus, we successfully reconstituted a portion of the HT biosynthetic pathway in HT non-accumulating N. benthamiana plants. This heterologous gene expression system will be useful for co-expressing candidate genes involved in downstream reactions in the HT biosynthetic pathway and for clarifying their in planta functions., (© 2023. The Author(s).)

Biofilm refers to a community of microorganisms that adhere to a substrate and play a crucial role in microbial pathogenesis and developing infections associated with medical devices. Enterobacter hormaechei and Klebsiella pneumoniae are classified as significant nosocomial pathogens within the ESKAPE category and cause diverse infections. In addition to their reputation as prolific biofilm formers, these pathogens are increasingly becoming drug-resistant and pose a substantial threat to the healthcare setting. Due to the inherent resistance of biofilms to conventional therapies, novel strategies are imperative for effectively controlling E. hormaechei and K. pneumoniae biofilms. This study aimed to assess the anti-biofilm activity of gallic acid (GA) against E. hormaechei and K. pneumoniae . The results of biofilm quantification assays demonstrated that GA exhibited significant antibiofilm activity against E. hormaechei and K. pneumoniae at concentrations of 4 mg mL -1 , 2 mg mL -1 , 1 mg mL -1 , and 0.5 mg mL -1 . Similarly, GA exhibited a dose-dependent reduction in violacein production, a QS-regulated purple pigment, indicating its ability to suppress violacein production and disrupt QS mechanisms in Chromobacterium violaceum. Additionally, computational tools were utilized to identify the potential target involved in the biofilm formation pathway. The computational analysis further indicated the strong binding affinity of GA to essential biofilm regulators, MrkH and LuxS, suggesting its potential in targeting the c-di-GMP and quorum sensing (QS) pathways to hinder biofilm formation in K. pneumoniae . These compelling findings strongly advocate GA as a promising drug candidate against biofilm-associated infections caused by E. hormaechei and K. pneumoniae.

Disturbance in the production and excretion of bile acid causes cholestatic liver disease. Liver cirrhosis is a disease that occurs if cholestasis continues. This study evaluated the protective effect of gallic acid (GA) on liver damage caused by biliary cirrhosis. Rats were randomly divided into 4 groups, each with 8 subjects: 1) control, 2) BDL, 3) BDL + GA 20, and 4) BDL + GA 30. The rats were anesthetized 28 days after the BDL, followed by collecting their blood and excising their liver. Their serum was used to measure liver enzymes, and the liver was used for biochemical analysis, gene expression, and histopathological analysis. Serum levels of liver enzymes, total bilirubin, liver Malondialdehyde level (MDA), expression of inflammatory cytokines and caspase-3, necrosis of hepatocytes, bile duct proliferation, lymphocytic infiltration, and liver fibrosis showed an increase in the BDL group compared to the control group ( p  < 0.05). In addition, BDL decreased the activity of liver antioxidant enzymes and glutathione (GSH) levels compared to the control group ( p  < 0.05). The groups receiving GA indicated a decrease in liver enzymes, total bilirubin, MDA, the expression of inflammatory cytokines and caspase-3, and a reduction in liver tissue damage compared to the BDL group ( p  < 0.05). The level of GSH in the BDL + GA 20 group showed a significant increase compared to the BDL group ( p  < 0.05). Moreover, it was found that GA, with its anti-fibrotic and anti-inflammatory properties, reduces liver damage caused by biliary cirrhosis.

Gallic acid is a powerful antioxidant with multiple therapeutic applications, usually obtained from the acidic hydrolysis of tannins produced by many plants. As this process generates a considerable amount of toxic waste, the use of tannases or tannase-producing microorganisms has become a greener alternative over the last years. However, their high costs still impose some barriers for industrial scalability, requiring solutions that could be both greener and cost-effective. Since Pseudomonas putida KT2440 is a powerful degrader of gallic acid, its metabolism offers pathways that can be engineered to produce it from cheap and renewable carbon sources, such as the crude glycerol generated in biodiesel units. In this study, a synthetic operon with the heterologous genes aroG4, quiC and pobA* was developed and expressed in P. putida, based on an in silico analysis of possible metabolic routes, resulting in no production. Then, the sequences pcaHG and galTAPR were deleted from the genome of this strain to avoid the degradation of gallic acid and its main intermediate, the protocatechuic acid. This mutant was transformed with the vector containing the synthetic operon and was finally able to convert glycerol into gallic acid. Production assays in shaker showed a final concentration of 346.7 ± 0.004 mg L -1 gallic acid after 72 h., (© 2022. The Author(s).)

The fermentation process has been widely used to improve plant-based foods' nutritional and nutraceutical properties. This study aimed to investigate and compare the impact of sourdough fermentation on the bioactive content and profile, antioxidant and antihypertensive activities, as well as the anti-inflammatory properties of fermented (FS) and non-fermented (NFS) flour from Tuscan Triticum dicoccum wheat (spelt) on tumor necrosis factor-alpha (TNF-α)-inflamed human intestinal epithelial cells (HT-29). FS showed significantly higher total phenolic and flavonoid content, in vitro and ex vivo antioxidant activities, and ACE-inhibitory activities than NFS. Gallic acid was identified by HPLC-DAD as the most representative polyphenol, followed by rutin, trans-ferulic acid, iso-quercitrin, and quercetin, in the fermented spelt sample. Instead, rutin and gallic acid were identified as the predominant compounds in the non-fermented ones. Moreover, FS exhibited a better protective effect on inflamed HT-29 cells by significantly counteracting the TNFα-induced alterations, lowering the expression of IL-8, COX-2, and ICAM-1 inflammatory mediator while enhancing antioxidant enzyme HO-1 gene expression. In conclusion, sourdough fermentation positively affected the nutraceutical and functional properties of spelt, which may represent a valuable ingredient for the formulation of functional foods and a key product for managing hypertension and inflammatory intestinal diseases.

Mucoadhesive hydrogels with multifunctional properties such as gastric acid resistance and sustained drug release in the intestinal tract are highly desirable for the oral treatment of inflammatory bowel diseases (IBDs). Polyphenols are proven to have great efficacies compared with the first-line drugs for IBD treatments. We recently reported that gallic acid (GA) was capable of forming a hydrogel. However, this hydrogel is prone to easy degradation and poor adhesion in vivo . To tackle this problem, the current study introduced sodium alginate (SA) to form a gallic acid/sodium alginate hybrid hydrogel (GAS). As expected, the GAS hydrogel showed excellent antiacid, mucoadhesive, and sustained degradation properties in the intestinal tract. In vitro studies demonstrated that the GAS hydrogel significantly alleviated ulcerative colitis (UC) in mice. The colonic length of the GAS group (7.75 ± 0.38 cm) was significantly longer than that of the UC group (6.12 ± 0.25 cm). The disease activity index (DAI) value of the UC group was (5.5 ± 0.57), which was markedly higher than that of the GAS group (2.5 ± 0.65). The GAS hydrogel also could inhibit the expression of inflammatory cytokines, regulating macrophage polarization and improving the intestinal mucosal barrier functions. All these results indicated that the GAS hydrogel was an ideal candidate for oral treatment of UC.

Gallic acid is a prevalent secondary plant metabolite distinguished as one of the most effective free-radical scavengers among phenolic acids. This compound is also known for its cytotoxic, anti-inflammatory, and antimicrobial activities. Bulk quantities of gallic acid are conventionally produced by acid hydrolysis of tannins, a costly and environmentally hazardous process. With the aim to develop more sustainable approaches, microbial bioproduction strategies have been attempted recently. To advance synthetic biology and metabolic engineering of microorganisms for gallic acid production, we characterize here a transcription factor-based inducible system Pp GalR/P PP&#95;RS13150 that responds to the extracellular gallic acid in a dose-dependent manner in Pseudomonas putida KT2440. Surprisingly, this compound does not mediate induction when Pp GalR/P PP&#95;RS13150 is used in non-native host background. We show that the activation of the inducible system requires gallate dioxygenase activity encoded by galA gene. The 4-oxalomesaconic acid, an intermediate of gallic acid-metabolism, is identified as the effector molecule that interacts with the transcription factor GalR mediating activation of gene expression. Introduction of galA gene along galR enables development of biosensors suitable for detection and monitoring of gallic acid extracellularly using non-native hosts such as E. coli and C. necator . Moreover, the P. putida -based biosensor's applicability is demonstrated by detecting and measuring gallic acid in extracts of Camellia sinensis leaves. This study reports the strategy, which can be applied for developing gallic acid biosensors using bacterial species outside Pseudomonas genus.

Background: Algal infestation in Korean lakes, rivers, and in agroecosystems is a catastrophic problem resulting in contaminated drinking and agricultural irrigation water. Developing allelochemical-based algicides has previously faced difficulties, including dosage requirements and chemical instability. Despite these challenges, these algicides have enormous potential for eco-friendly use. This study presents the efficient use of tannin derivatives as antialgal chemicals modeled on a tannin-rich stem extract of Rhus chinensis in a thermal processing application., Results: Tannic acids are the key component of algal necrosis in R. chinensis stem extract, and although heat extraction from the stem increased the crude extraction yield 1.8-fold, the procedure induced the conversion of tannic acids to gallic acid, resulting in lower antialgal activity. Gallotannin showed stronger antialgal activity (The 50% lethal dosage (LD 50 )= 44.6 mg L -1 ) than gallic acid (LD 50  = 99.2 mg L -1 ), and the nonheated extract exhibited 3.7-fold lower LD 50 (0.66 g L -1 ) than the heated extract (LD 50  = 2.45 g L -1 ), resulting in 2.6-fold higher content of gallotannin., Conclusion: These results demonstrate that heat treatment of R. chinensis stems during the extraction process is not beneficial to algal control because of the acceleration of thermal tannin degradation, despite it showing higher crude extract yields. Therefore, it is suggested extraction processes minimizing the loss of tannic acids should be the preferred methods used to develop tannin-based natural algicides for controlling algal infestation. Tannic acids showed higher toxicity into necrosis of M. aeruginosa than gallic acid where heat-processed extraction of R. chinensis stems produces more gallic acid content resulting in thermal degradation of tannic complexes than the extraction of nonthermal treatment. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Psoriasis and atopic dermatitis (AD) are characterized by enhanced skin inflammation, which results in hyperproliferation and the recruitment of immune cells into the skin. For that reason, it is needed a chemical capable to reduce cell proliferation and the recruitment of cells. The search for new molecules for therapeutic skin treatment mainly focuses on the antioxidant and anti-inflammatory properties, highlighting the rheological properties of polymeric polypeptides. We studied L-arginine (L-Arg) grafted (-g-) to enzymatic poly(gallic acid) (PGAL). The latter is a multiradical antioxidant with greater properties and thermal stability. The derivative was enzymatically polymerized in an innocuous procedure. The poly(gallic acid)-g-L-Arg molecule (PGAL-g-L-Arg) inhibits bacterial strains which also have been involved in the progression of psoriasis and AD. However, it is important to analyze their biological effect on skin cells. The cell viability was analyzed by calcein/ethidium homodimer assays and crystal violet. The proliferation and cell attachment were determined by a curve of time and quantitation of the optical density of crystal violet. To analyze the cell migration a wound-healing assay was performed. This synthesis demonstrates that it is not cytotoxic at high concentrations (250 μg/mL). We observed a decrease in the proliferation, migration, and adhesion of dermal fibroblasts in vitro but the compound could not avoid the increase of reactive oxygen species in the cell. Based on our findings, PGAL-g-L-Arg is a promising candidate for treating skin diseases such as psoriasis and AD where decreasing the proliferation and cell migration could help to avoid inflammation.

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.

Due to the increasing use of silica nanoparticles (SiNPs), their possible toxic effects on human health have undoubtedly been considered. Previous studies proved that SiNPs induced oxidative stress. Reactive oxygen species (ROS) and oxidative stress disrupt cell function and decrease insulin secretion. Therefore, this study intended to assess the effects of SiNPs on oxidative stress and insulin secretion and also the protective effects of gallic acid (GA) and gallic acid nanoparticles (NP-GA) on pancreatic β-islets. In this study, the mice islets were separated and pretreated with various concentrations of GA and NP-GA then treated with a single dose of SiNPs. The cell viability of islets examined by MTT assay and also the levels of ROS, malondialdehyde (MDA), glutathione (GSH); activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and insulin secretion were evaluated. The results of MTT assay showed that SiNPs reduced islet viability in a dose-dependent manner and also insulin secretion, induced the formation of ROS, augmented MDA amounts, and decreased GSH levels, SOD, GPx, and CAT activities. Furthermore, pretreatment of islets with GA and NP-GA significantly returned these alterations at low dose. These findings suggested that SiNPs induced oxidative stress in the pancreatic islets, which could be one of the reasons for the decrease in insulin secretion and inducing diabetes. This study also showed that low doses of GA and NP-GA boosted the antioxidant defense system in the pancreatic β-islets, preventing oxidative stress and, consequently, the progression of diabetes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The overexpression of efflux pumps is one of the strategies used by bacteria to resist antibiotics and could be targeted to circumvent the antibiotic crisis. In this work, a series of trimethoxybenzoic acid derivatives previously described as antifouling compounds was explored for potential antimicrobial activity and efflux pump (EP) inhibition. First, docking studies on the acridine resistance proteins A and B coupled to the outer membrane channel TolC (AcrAB-TolC) efflux system and a homology model of the quinolone resistance protein NorA EP were performed on 11 potential bioactive trimethoxybenzoic acid and gallic acid derivatives. The synthesis of one new trimethoxybenzoic acid derivative (derivative 13 ) was accomplished. To investigate the potential of this series of 11 derivatives as antimicrobial agents, and in reverting drug resistance, the minimum inhibitory concentration was determined on several strains (bacteria and fungi), and synergy with antibiotics and EP inhibition were investigated. Derivative 10 showed antibacterial activity against the studied strains, derivatives 5 and 6 showed the ability to inhibit EPs in the acrA gene inactivated mutant Salmonella enterica serovar Typhimurium SL1344, and 6 also inhibited EPs in Staphylococcus aureus 272123. Structure-activity relationships highlighted trimethoxybenzoic acid as important for EP inhibitory activity. Although further studies are necessary, these results show the potential of simple trimethoxybenzoic acid derivatives as a source of feasible EP inhibitors.

HPLC-UV was used to compare the major constituents of two Pelargonium × hortorum cultivars and Pelargonium sidoides root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in P. × hortorum root extracts. The antibacterial activity of these extracts was screened against 19 Pseudomonas aeruginosa clinical isolates. P. × hortorum root extracts showed the lowest MIC values (512-1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on las I and las R genes expression using qRT-PCR and simultaneous docking against Las R protein was explored. The combination downregulated las I and las R gene expression in eight and six P. aeruginosa isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.

As a tropical medicinal plant, Sonneratia apetala is mainly distributed in the southeast coastal areas of China. Recently, the hypouricemic effect of Sonneratia apetala leaves and branches (SAL) has been reported, but the active compound and its mechanism are unclear. Thus, this study aims to explore the effective fraction of SAL and the mechanism of its active compound on uric acid formation and excretion. SAL was extracted with ethyl acetate and concentrated to obtain solvent-free extracts (SAL-EA). The remains fraction (SAL-E) and the supernatant fraction (SAL-S) of SAL resulting from water extraction and alcohol precipitation were collected and dried. The effects of different fractions were explored on hyperuricemic mice. SAL-S showed excellent activities in decreasing the levels of uric acid (UA), blood urea nitrogen (BUN), and creatinine (CRE) in serum and in attenuating kidney damage. Then, the active compound gallic acid (GA) identified by HPLC was assayed for its mechanism of regulating uric acid metabolism in hyperuricemic mice. The hypouricemic effect of GA was probably associated with the downregulation of URAT1 and GLUT9, upregulation of ABCG2 and decreased activities of adenosine deaminase (ADA) and xanthine oxidase (XOD). Moreover, GA suppressed the level of MDA, IL-6, IL-1β, TNF-α, TGF-β1, COX-2 and cystatin-C (Cys-C), and enhanced the activities of SOD, GSH-Px, CAT, and Na + -K + -ATPase (NKA) in the kidneys. These results indicated that GA protects against hyperuricemia-induced kidney injury via suppressing oxidative stress and inflammation as well as decreasing the serum levels of UA by regulating urate transporters.

Seabuckthorn extract is rich in bioactive compounds and well known for its health benefits. The study investigated the effect of seabuckthorn leaf extract on browning of fresh-cut potatoes. The results showed that seabuckthorn leaf extract significantly inhibited the browning of fresh-cut potatoes compared with seabuckthorn fruit extract. Catechin, hypericin, gallic acid, casuarinin and isorhamnetin were main components in seabuckthorn leaf extract. Further research revealed that seabuckthorn leaf extract competitively inhibited polyphenol oxidase (PPO) with IC 50 value of 0.7 mg/mL. Molecular docking indicated that gallic acid stably bound to the active site of PPO, while isorhamnetin had low affinity on PPO. These results also demonstrated that seabuckthorn leaf extract inhibited browning of fresh-cut potatoes by reducing activities of peroxidase and phenylalanine ammonia-lyase, decreasing contents of phenolics and elevating antioxidant capacity. In addition, synergistic anti-browning effect was found with casuarinin, isorhamnetin, gallic acid and pedunculagin., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughout Northern America and Europe. This pathogen, if not treated in a timely manner with antibiotics, can cause persisting and debilitating health outcomes. In the search for novel agents against B. burgdorferi , we investigated a phenolic compound-gallic acid-for its anti- Borrelia and anti-inflammatory effects. Our results showed its biocidal effect starting from 100 μg/mL against active spirochetes, persisters/round-shaped bodies, and biofilm like aggregates of B. burgdorferi sensu stricto . Activation of macrophages by live B. burgdorferi also resulted in a robust NFκB-dependent proinflammatory responses seen in increased production of cytokines. Using human CD14+ macrophages in vitro , we showed that CD14+ adaptor and phosphorylated p65 molecule are impeded at nonbiocidal and noncytotoxic concentrations of gallic acid, resulting in the inhibition of both expression and secretion of cytokines IL1β, IL6, and TNFα. Our findings demonstrate efficacy of gallic acid against B. burgdorferi and provide potential mechanistic insight into its TLR2/CD14+-NFκB mediated mode of action. Further studies on the potential of gallic acid as a safe and effective compound against Borrelia- caused infection are warranted.

A tannase-positive Bacillus gottheilii M2S2 and Bacillus cereus M1GT were co-cultivated for the production of gallic acid using tannic acid as the sole carbon source through submerged fermentation. Taguchi orthogonal array of design of experimental methodology was used to estimate the influence and significance of tannic acid concentration, glucose concentration, agitation speed, and inoculum size on the gallic acid production in a shake flask. Among all the factors, agitation speed contributed the highest for gallic acid production (28.28%), followed by glucose concentration (21.59%), inoculum size (19.6%), tannic acid concentration (19.54%), and pH (11.09%). Validation experiments were executed at the found optimized conditions which resulted in a 6.36-fold increase in gallic acid yield compared to unoptimized conditions. Further, the kinetics of growth, tannic acid degradation, and gallic acid yield were evaluated at the optimized conditions. The kinetic parameters Y  x/s , Y  p/s , and Y  p/x were determined as 0.292 mg of cells/mg of tannic acid, 22.2 µg of gallic acid/mg of tannic acid, and 70.76 µg of gallic acid/mg of cells with a growth rate of 0.273 h  -1 after 24 h of fermentation. Finally, the antimicrobial activity of the product gallic acid was investigated against food-borne pathogenic E. coli, S. aureus, and Serriatia marcescens and showed a zone of inhibition of 2 cm, 1.6 cm, and 1.3 cm, respectively, using the agar disc diffusion technique. Thus, the cost-effective bioproduct gallic acid proved to be potentially effective to control food poisoning diseases and preserve foodstuff., (© 2022. The Author(s).)

Gallic acid is a phenolic compound that exhibits antibacterial, antioxidative and anti-inflammatory functions. In a previous study, we found that dietary supplementation with gallic acid decreased incidence of diarrhoea and protected intestinal integrity in weaning piglets. However, the underlying mechanism remains unclear. Here, a pig intestinal epithelial cell line (IPEC-J2) was used as an in vitro model to explore the antioxidant and anti-inflammatory capacity of gallic acid. IPEC-J2 cells were stimulated with hydrogen peroxide (H 2 O 2 ) and lipopolysaccharide (LPS) to establish oxidative and inflammatory models, respectively. Results showed that H 2 O 2 significantly decreased catalase (CAT) secretion and CAT mRNA abundance in the cells (p < 0.05), while pretreatment with gallic acid did not prevent the decrease in CAT expression induced by H 2 O 2 . However, gallic acid pretreatment mitigated the increased expression of the tumour necrosis factor-α and interleukin-8 genes caused by LPS in IPEC-J2 cells (p < 0.05). In addition, pretreatment with gallic acid significantly suppressed phosphorylation of NF-κB and IκBα in LPS-stimulated IPEC-J2 cells. Moreover, LPS stimulation decreased the protein abundance of zona occludens 1 (ZO-1) and occludin, while pretreatment with gallic acid preserved expression level of tight junction proteins ZO-1 and occludin in LPS-stimulated IPEC-J2 cells (p < 0.05). In conclusion, gallic acid may mitigate LPS-induced inflammatory responses by inhibiting the NF-κB signalling pathway, exerting positive effects on the barrier function of IPEC-J2 cells., (© 2021 Wiley-VCH GmbH.)

Polyphenolic compounds are a diverse group of natural compounds that interact with various cellular proteins responsible for cell survival, differentiation, and apoptosis. However, it is yet to be established how these compounds interact in myeloid cells during their differentiation and the molecular and intracellular mechanisms involved. Osteoclasts are multinucleated cells that originate from myeloid cells. They resorb cartilage and bone, maintain bone homeostasis, and can cause pathogenesis. Autophagy is a cellular mechanism that is responsible for the degradation of damaged proteins and organelles within cells and helps maintain intracellular homeostasis. Imbalances in autophagy cause various pathological disorders. The current study investigated the role of several polyphenolic compounds, including tannic acid (TA), gallic acid (GA), and ellagic acid (EA) in the regulation of osteoclast differentiation of myeloid cells. We demonstrated that polyphenolic compounds inhibit osteoclast differentiation in a dose-dependent manner. Quantitative real-time PCR, immunocytochemistry, and western blotting revealed that osteoclast markers, such as NFATc1, Cathepsin K, and TRAP were inhibited after the addition of polyphenolic compounds during osteoclast differentiation. In our investigation into the molecular mechanisms, we found that the addition of polyphenolic compounds reduced the number of autophagic vesicles and the levels of LC3B, BECN1, ATG5, and ATG7 molecules through the inactivation of Akt, thus inhibiting the autophagy process. In addition, we found that by decreasing intracellular calcium and decreasing ROS levels, along with decreasing mitochondrial membrane potential, polyphenolic compounds inhibit osteoclast differentiation. Together, this study provides evidence that polyphenolic compounds inhibit osteoclast differentiation by reducing ROS production, autophagy, intracellular Ca 2+ level, and mitochondrial membrane potentials.

Gallic acid (GA) is a secondary metabolite found in plants. It has the ability to cross the blood-brain barrier and, through scavenging properties, has a protective effect in a brain insult model. Alcohol metabolism generates reactive oxygen species (ROS); thus, alcohol abuse has a deleterious effect on the brain. The zebrafish is a vertebrate often used for screening toxic substances and in acute ethanol exposure models. The aim of this study was to evaluate whether GA pretreatment (24 h) prevents the changes induced by acute ethanol exposure (1 h) in the purinergic signaling pathway in the zebrafish brain via degradation of extracellular nucleotides and oxidative stress. The nucleotide cascade promoted by the nucleoside triphosphate diphosphohydrolase (NTPDase) and 5'-nucleotidase was assessed by quantifying nucleotide metabolism. The effect of GA alone at 5 and 10 mg L -1 did not change the nucleotide levels. Pretreatment with 10 mg L -1 GA prevented an ethanol-induced increase in ATP and ADP levels. No significant difference was found between the AMP levels of the two pretreatment groups. Pretreatment with 10 mg L -1 GA prevented ethanol-enhanced lipid peroxidation and dichlorodihydrofluorescein (DCFH) levels. The higher GA concentration was also shown to positively modulate against ethanol-induced effects on superoxide dismutase (SOD), but not on catalase (CAT). This study demonstrated that GA prevents the inhibitory effect of ethanol on NTPDase activity and oxidative stress parameters, thus consequently modulating nucleotide levels that may contribute to the possible protective effects induced by alcohol and purinergic signaling., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Nannochloropsis oculata is a marine microalgal species with a great potential as food or feed due to its high pigment, protein and eicosapentaenoic acid contents. However, for such an application to be realized on a large scale, a biorefinery approach is necessary due to the high cost of microalgal biomass production. For example, techno economic analyses have suggested the co-production of food or feed with antioxidants, which can be extracted and supplied separately to the market. The aim of this study was to investigate the effect of cultivation conditions on the antioxidant capacity of Nannochlosopsis oculata extracts, derived with ultrasound-assisted extraction at room temperature, as well as the proximate composition and fatty acid profile of the biomass. A fractional factorial approach was applied to examine the effects of temperature (20-35 °C), pH (6.5-9.5) and light period (24:0, 12:12). At the end of each run, biomass was collected, washed with 0.5M ammonium bicarbonate and freeze-dried. Antioxidant capacity as gallic acid equivalents as well as pigment content were measured in the ethanolic extracts. Optimal conditions were different for productivity and biomass composition. Interesting results regarding the effect of light period (LP) and pH require further investigation, whereas the effect of moisture on the extraction process was confounded with biomass composition. Finally, further data is provided regarding the relation between chlorophyll content and apparent phenolic content using the Folin-Ciocalteu assay, in agreement with our previous work.

Gallic acid (GA) is a widespread naturally occurring phenolic acid and one of the main active monomers that forms polyphenols such as tannins. In recent years, GA has been found as a potential regulator in lipid metabolism. However, effects and possible mechanisms of GA on cell growth and lipid metabolism of bovine subcutaneous adipocytes remain unknown. In this study, we investigated whether GA could affect proliferation and adipogenesis of subcutaneous adipocyte in beef cattle. We found that GA possesses inhibitive effects on proliferation and adipogenesis of bovine subcutaneous adipocyte via activating the metabolic master factor AMP-activated protein kinase alpha (AMPKα) to promote programmed cell death and lipolysis. The findings prove GA is a key substance to inhibit proliferation and adipogenesis of bovine subcutaneous adipocyte in vitro . Further in vivo study needs conducted to verify the reductive effects of GA on subcutaneous fat in beef cattle.

Objective: This study aimed to investigate the effects of gallic acid and silymarin against nephrotoxicity and hepatotoxicity caused by cisplatin., Materials and Methods: In the study, 56 Wistar Albino rats were equally divided into eight groups. Group 1 was the control group; group 2 was the group receiving cisplatin; group 3 was the group receiving cisplatin + gallic acid; group 4 was the group receiving cisplatin + silymarin; group 5 was the group receiving cisplatin + silymarin + gallic acid; group 6 was the group receiving silymarin; group 7 was the group receiving gallic acid; group 8 was the group receiving gallic acid + silymarin. AST, ALT, urea, creatinine, albumin, globulin, and total protein levels were measured at the end of the study. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione (GSH), and 8-hydroxy-2'-deoxyguanosine (8OH-dG) levels were measured in kidney and liver tissues. Additionally, histopathological evaluations of the tissues were also performed., Results: In kidney and liver tissues, cisplatin significantly increased MDA and 8-OHdG levels compared with treatment groups ( p < 0.05). Silymarin-treated group significantly increased the SOD activity and GSH amount in the liver tissue compared with the cisplatin-treated group ( p < 0.05). Gallic acid significantly increased CAT activity compared with the cisplatin-treated group ( p < 0.05). It was determined that the cisplatin-treated group significantly decreased CAT and SOD activity compared with the control group ( p > 0.05). Gallic acid showed a significant increase in CAT and SOD activity in kidney tissue compared with the cisplatin-treated group ( p < 0.05)., Conclusion: As a result, it was observed that gallic acid silymarin had a protective effect on cisplatin-induced nephrotoxic and hepatotoxic effects., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Duygu Doğan et al.)

The objective of this study was to evaluate the effects of feeding gallic acid on the growth, nutrient digestibility, plasma metabolites, rumen fermentation, and bacterial community in the rumen fluid and feces of preweaning calves. Thirty-six female Holstein calves with similar ages (means ± SD; 3.1 ± 1.39 d) and body weights (40.8 ± 2.87 kg) were randomly assigned to receive 3 treatments. Calves were fed 1 of 3 treatments as follows: basal diet with no gallic acid (control), 0.5 g/kg gallic acid in starter diet (low), and 1 g/kg gallic acid in starter diet (high). The results showed that feeding gallic acid increased growth by improving the starter intake and average daily gain of the calves. The fecal score tended to decrease in a linear manner with the addition of gallic acid. Total-tract apparent protein digestibility tended to increase linearly with feeding gallic acid. Feeding gallic acid led to a linear increase in the plasma total protein and β-hydroxybutyrate levels. In addition, feeding gallic acid linearly increased catalase and total antioxidant capacity levels and decreased malondialdehyde and tumor necrosis factor-α concentrations. The concentrations of total volatile fatty acids, propionate, butyrate, and valerate in the rumen fluid increased linearly with the addition of gallic acid, resulting in a linear pH reduction. Feeding gallic acid linearly increased the relative abundances of Prevotella&#95;1, Saccharofermentans, and Prevotellaceae&#95;UCG-001 and linearly decreased the relative abundance of Prevotella&#95;7 in the rumen fluid. The Shannon index of ruminal bacterial communities linearly increased by feeding gallic acid. Feeding gallic acid linearly increased the relative abundances of Ruminococcaceae&#95;UCG-005, Bacteroides, and Christensenellaceae&#95;R-7&#95;group in the feces. In summary, feeding gallic acid improved growth, antioxidant function, and rumen fermentation and altered the bacterial community in the rumen fluid and feces of preweaning dairy calves., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1 H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor β((ERβ) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics., (Copyright © 2021. Published by Elsevier B.V.)

Poor prognosis and metastasis have been recognized as the major cause of breast cancer related deaths worldwide. Recent experimental evidence has shown that Hsp90, the prime chaperone, is overexpressed in many cancers and is responsible if reducing the 5-year survival rate of cancer patients. Therefore, targeted inhibition of Hsp90 may be a new and effective way to target cancer as well as enhancing therapeutic outcomes. In the present study, screening and simulation of potential natural compounds result in the identification of theaflavin-3-gallate as a promising inhibitory compound of Hsp90. Further in-vitro validation of the cytotoxic effect of theaflavin-3-gallate in human breast carcinoma cell line MCF7 and normal cell line MCF10A revealed that theaflavin-3-gallate significantly inhibited the cell proliferation of MCF7 cells whereas no cytotoxic effect was observed on MCF10A cells. We also found that theaflavin-3-gallate significantly induced programmed cell death by arresting cells in the G2/M phase of the cell cycle. A significant decrease in cell migration and colony formation by theaflavin-3-gallate treatment was also observed in MCF7 cells. Furthermore, theaflavin-3-gallate significantly downregulated the mRNA expression patterns of the HSP90, MMP9, VEGFA, and SPP1 genes. Collectively, our results demonstrated theaflavin-3-gallate as a potential natural Hsp90 inhibitor that can be used to enhance the therapeutic efficacy of existing breast cancer therapies and improve overall survival of breast cancer patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Inflammation is a complex mechanism with an objective to destroy and eliminate the invading microorganisms. During acute inflammation, the neutrophils are the major cells involved in this process and, although they defend the organism, must die to not generate damage. The two major mechanisms that drive neutrophils to death are: apoptosis and a novel mechanism recently discovered denominated NETosis. This process is a "suicidal mechanism", in which the cells release "neutrophil extracellular traps" (NETs) during the inflammatory response. Octyl gallate (OG) is one of the gallic acid derivates, with several protective effects, such as antioxidant and anti-inflammatory in cancer models. Thus, this study aimed to investigate the action of OG on the proliferation of lymphocytes, neutrophils activation, and its effectiveness in an experimental sepsis model., Methods: Lymphocytes and neutrophils were obtained from healthy donors. Cell viability, apoptosis, NETs release and antioxidant capacity of OG were observed. In addition, survival was evaluated in an experimental model of sepsis in C57BL/6 mice., Results: Our study demonstrated, for the first time, that the OG can act as an inhibitor of reactive oxygen species (ROS) release, NETs formation in primary human neutrophils and, modulates the lipopolysaccharide (LPS) effect in neutrophil apoptosis. The OG also inhibited peripheral blood mononuclear cells (PBMCs) proliferation in vitro. Despite the positive results, we did not observe an increase in the survival of septic animals., Conclusions: The pharmacological potential of OG, modulating activation of neutrophils and lymphocytes, suggests the use as an adjuvant therapeutic strategy in inflammatory diseases., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects., Objective: The current research aimed at evaluating the GA effect on CP-related renal toxicity., Methods: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue., Results: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect., Conclusion: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Diabetes mellitus (DM) is a severe chronic metabolic disease with increased mortality and morbidity. The pathological progression of DM is intimately connected with the formation and activation of oxidative stress (OS). Especially, the involvement of OS with hyperglycemia, insulin resistance, and inflammation has shown a vital role in the pathophysiological development of DM and related complications. Interestingly, accumulating studies have focused on the exploration of natural antioxidants for their improvement on DM. Of specific interest is gallic acid (GA), which is rich in many edible and herbal plants and has progressively demonstrated robust antioxidative and anti-inflammatory effects on metabolic disorders. To provide a better understanding of its potential therapeutic impacts and enhancement of human health care, the available research evidence supporting the effective antidiabetic properties of GA and relevant derivatives are needed to be summarized and discussed, with emphasis on its regulation on OS and inflammation against DM. This review aims to highlight the latest viewpoints and current research information on the role of OS in diabetes and to provide scientific support for GA as a potential antihypoglycemic agent for DM and its complications.

Phenolipids such as alkyl gallates (A-GAs) have been approved by food industry as non-toxic antioxidant additives. However, their digestion and absorption mechanisms in the intestine have not yet been clarified. In this research, the hydrolysis and transport characteristics of A-GAs with fatty alcohols of various chain lengths (C1:0, C2:0, C3:0, C4:0, C8:0, C12:0 and C16:0) were estimated by the everted-rat-gut-sac model (ERGSM) for the first time. High-performance liquid chromatography measurements proved that measurable peaks corresponding to methyl gallate (G-C1:0), ethyl gallate (G-C2:0), propyl gallate (G-C3:0) and butyl gallate (G-C4:0) were discovered in the serosal fluids, which showed the short-chain alkyl gallates can cross the membrane in the form of esters. Besides, all A-GAs were hydrolyzed to GA in the mucosal solution, which contributed evidently to the transport of GA across the membrane of the small intestine. Meanwhile, the hydrolysis rate of A-GAs and transport rate of GA initially increased and then decreased with the chain length, exhibiting a maximum for octyl gallate (G-C8:0). In general, all A-GAs have the behavior of sustained-release. In consequence, the production of A-GAs should be an effective method to extend action time and further increases biological activities of GA.

The current study aims at the functional and kinetic characterization of protocatechuate (PCA) 4,5-dioxygenase (PcaA) from Pseudarthrobacter phenanthrenivorans Sphe3. This is the first single subunit Type II dioxygenase characterized in Actinobacteria. RT-PCR analysis demonstrated that pca A and the adjacent putative genes implicated in the PCA meta -cleavage pathway comprise a single transcriptional unit. The recombinant PcaA is highly specific for PCA and exhibits Michaelis-Menten kinetics with K m and V max values of 21 ± 1.6 μM and 44.8 ± 4.0 U × mg -1 , respectively, in pH 9.5 and at 20 °C. PcaA also converted gallate from a broad range of substrates tested. The enzymatic reaction products were identified and characterized, for the first time, through in situ biotransformation monitoring inside an NMR tube. The PCA reaction product demonstrated a keto-enol tautomerization, whereas the gallate reaction product was present only in the keto form. Moreover, the transcriptional levels of pca A and pca R (gene encoding a LysR-type regulator of the pathway) were also determined, showing an induction when cells were grown on PCA and phenanthrene. Studying key enzymes in biodegradation pathways is significant for bioremediation and for efficient biocatalysts development.

The aim of the study was to investigate changes in the content of biologically active compounds during the fermentation and aging of natural meads with the addition of three Cornelian cherry juices from three cultivars: 'Koralovyi', 'Podolski' and 'Yantarnyi', in the amount of 10% v / v . After the fermentation process the content of gallic and ellagic acids significantly increased, in relation to wort. Whereas the greatest losses were observed among unstable anthocyanins. The three-month aging process also reduced the content of the analyzed compounds except for ellagic acid, the content of which increased by up to 90%. The content of biologically active compounds, including iridoids and antioxidant phenolics, are constantly changing in the process of fermentation and aging of fruit meads. The studies proved that the addition of Cornelian cherry juice allows significantly enriched classic meads with new biologically active compounds, such as: exceptional iridoids (loganic acid, cornuside, loganine, sweroside), flavonols, phenolic acids and anthocyanins.

Aims: To isolate, identify and characterize phenolic acid-degrading bacteria and reduce plant growth inhibition caused by phenolic acids., Methods and Results: A total of 11 bacterial isolates with high phthalic acid (PA)-degrading ability were obtained using mineral salt medium (MSM) medium containing PA as sole carbon source. These isolates were identified as Arthrobacter globiformis, Pseudomonas putida and Pseudomonas hunanensis by sequence analyses of the 16S rRNA gene. Among them, five Pseudomonas strains could also effectively degrade ferulic acid (FA), p-hydroxybenzoic acid (PHBA) and syringic acid (SA) in MSM solution. P. putida strain 7 and P. hunanensis strain 10 showed highly efficient degradation of PA, SA, FA and PHBA, and could reduce their inhibition of lily, watermelon, poplar and strawberry seedling growth in soils respectively. These two strains could promote plant growth in soil with phenolic acids., Conclusions: In this study, bacterial strains with highly efficient phenolic acid-degrading abilities could not only effectively reduce the autotoxicity of phenolic acids on plants but also were able to promote plant growth in soil with phenolic acids., Significance and Impact of the Study: In this study, Pseudomonas can promote plant growth while degrading phenolic acids. Our results provide new choices for the biological removal of autotoxins., (© 2020 The Society for Applied Microbiology.)

The iron gall ink-triggered chemical corrosion of hand-written documents is a big threat to Western cultural heritages, which was demonstrated to result from the iron gall (GA-Fe) chelate-promoted reactive oxygen species generation. Such a phenomenon has inspired us to apply the pro-oxidative mechanism of GA-Fe to anticancer therapy. In this work, we construct a composite cancer nanomedicine by loading gallate into a Fe-engineered mesoporous silica nanocarrier, which can degrade in acidic tumor to release the doped Fe 3+ and the loaded gallate, forming GA-Fe nanocomplex in situ. The nanocomplex with a highly reductive ligand field can promote oxygen reduction reactions generating hydrogen peroxide. Moreover, the resultant two-electron oxidation form of GA-Fe is an excellent Fenton-like agent that can catalyze hydrogen peroxide decomposition into hydroxyl radical, finally triggering severe oxidative damage to tumors. Such a therapeutic approach by intratumoral synthesis of GA-Fe nano-metalchelate may be instructive to future anticancer researches.