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Nature is a valuable source of anti-oxidants that have a health-promoting effect by inhibiting various undesirable changes leading to cell degradation and, consequently, potential disease ailments. One of them is gallic acid which has been used as a healing agent since ancient times. Currently, due to various beneficial properties, this compound is considered to be one of the main phenolic acids of great importance in numerous industries. It is commonly used as a substance protecting against the harmful effects of UV radiation, an astringent in cosmetic preparations, and a preservative in food products. Therefore, gallic acid is now deemed essential for both human health and industry. Increasingly better methods of its isolation and analysis are being developed, and new solutions are being sought to increase its production. This review, presenting a concise characterization of gallic acid, updates the knowledge about its various biological activities and methods used for its isolation and determination, including chromatographic and non-chromatographic methods.

A dual-responsive hydrogel (pH/temperature) was developed from a thermos-responsive polymer, pluronic F-127 (PF127), and pH-responsive polymers, N,N,N -trimethyl chitosan (TMC) and polyethylene glycolated hyaluronic acid (PEG-HA). Gallic acid, the principal component of the traditional Chinese drug Cortex Moutan was loaded into the hydrogel (PF127/TMC/PEG-HA) for possible application in textile-based transdermal therapy as Cortex Moutan has been proven to be an effective drug for the treatment of atopic dermatitis (AD). TMC and PEG-HA were synthesized, characterized ( 1 H-NMR and FTIR), and added to the formulations to enhance drug release from the hydrogels, and increase the drug targeting of the carriers. The thermo-responsive properties of the hydrogel were assessed by dynamic viscosity analysis and the tube inversion method, and the pH-responsiveness of the formulation was determined by changing the pH of the external media. Rheology study of the hydrogels showed that complex viscosity and storage/loss moduli for PF127/TMC/PEG-HA hydrogel formulation are higher than PF127 hydrogel. The microstructure analysis by reflection SAXS indicated similar type of frozen inhomogeneity of hydrogel formulations. Various characterizations such as FTIR, SEM, TEM, zeta potential, and degradation of the hydrogel formulation indicated that the PF127/TMC/PEG-HA hydrogel showed better physico-chemical properties and morphology than did the PF127 hydrogel, and drug release was also higher for the PF127/TMC/PEG-HA hydrogel than for PF127. The drug release from hydrogels followed more closely first-order rate model than other rate models.

D-galactose by instigating oxidative stress, inflammation, and degenerative changes, causes neurological problems, i.e., anxiety. Zinc oxide (ZnO)-gallic acid NPs were used to evaluate behavioral, biochemical, neurochemical, and histopathological studies following D-galactose administration in rats. Thirty animals were alienated into five sets (n = 6) i.e., control, D-galactose (300 mg/kg/mL), D-galactose + gallic acid (50 mg/mL/kg), D-galactose + ZnO NPs (10 mg/mL/kg), and D-galactose + ZnO-gallic acid NPs (10 mg/mL/kg). For 28 days, the animals were given their respective treatments intraperitoneally once a day. The anxiety-like behavior was evaluated following the treatment period using behavioral tests, i.e., light–dark and elevated-plus-maze activities. The hippocampus was isolated for biochemical, neurochemical, and histopathological studies. Results showed that ZnO-gallic acid NPs normalize the anxiety-like behavior induced by D-galactose administration. D-galactose induced a reduction in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), increased oxidative-stress markers (malondialdehyde), and elevated inflammatory markers (interleukin-1 and tumor necrosis factor-α). It also impaired serotonergic metabolism and the responsiveness of 5-HT1A receptors, along with causing morphological alterations in the hippocampus. ZnO-gallic acid NPs prevented these effects. These results underscore the protective effects of ZnO-gallic acid NPs against D-galactose-induced negative influences. The present finding suggested that ZnO-gallic acid NPs may be used as a potential agent to treat D-galactose-induced psychiatric illnesses such as anxiety through their antioxidant, anti-inflammatory, and neuromodulatory potential.

Potential effects of tea and its constituents on SARS-CoV-2 infection were assessed in vitro. Infectivity of SARS-CoV-2 was decreased to 1/100 to undetectable levels after a treatment with black tea, green tea, roasted green tea, or oolong tea for 1 min. An addition of (−) epigallocatechin gallate (EGCG) significantly inactivated SARS-CoV-2, while the same concentration of theasinensin A (TSA) and galloylated theaflavins including theaflavin 3,3′-di-O-gallate (TFDG) had more remarkable anti-viral activities. EGCG, TSA, and TFDG at 1 mM, 40 µM, and 60 µM, respectively, which are comparable to the concentrations of these compounds in tea beverages, significantly reduced infectivity of the virus, viral RNA replication in cells, and secondary virus production from the cells. EGCG, TSA, and TFDG significantly inhibited interaction between recombinant ACE2 and RBD of S protein. These results suggest potential usefulness of tea in prevention of person-to-person transmission of the novel coronavirus.

Zein/phospholipid composite nanoparticles (CNPs) were developed as a delivery platform for gallic acid (GA), a polyphenolic compound with reported preclinical antifibrotic activities. However, the therapeutic applicability of GA is hampered owing to its low bioavailability and rapid clearance. Accordingly, we developed GA-loaded CNPs. The effect of their size, surface charge and targeting strategies was investigated and optimized, with the aim of enhancing their ability to deliver GA to the activated hepatic stellate cells (aHSCs) in order to suppress hepatic fibrosis progression. Different CNP systems were prepared and characterized with regard to their particle size, zeta potential, and GA entrapment efficiency (EE%). Also, they were statistically optimized via response surface methodology. The optimized systems were investigated with regard to their in vitro GA release, in vitro efficacy on aHSCs, and in vivo biodistribution in healthy rats. The GA-loaded cationic CNPs coupled with vitamin A (GA-CACNP/VA; 192 nm) showed high GA EE% (60% w/w), highest cellular internalization via active targeting, and more selective hepatic distribution, relative to free GA solution, GA-loaded anionic, and GA-loaded cationic systems. Furthermore, GA-CACNP/VA markedly triggered the apoptosis of aHSCs, repressed collagen deposition, and inhibited HSCs' activation to a lesser extent. The GA-CACNP/VA was shown to be a promising candidate for specific and controlled delivery of GA to aHSCs, which may provide an effective antifibrotic therapeutic approach.

Fu brick tea is a unique post-fermented tea product which is fermented with microorganism during the manufacturing process. Metabolic analysis showed that most metabolites content were decreased during the manufacturing process of Fu brick tea, except GA (gallic acid). Illumina MiSeq sequencing of ITS gene amplicons was applied to analyze the fungal community succession. The genera Aspergillus , Cyberlindnera and Candida were predominant at the early stage of manufacturing process (from “primary dark tea” to “fermentation for 3 days”), but after the stage of “fermentation for 3 days” only Aspergillus was still dominated, and maintain a relatively constant until to the end of manufacturing process. The effects of metabolites on the structure of the fungal community were analyzed by redundancy analysis (RDA) and variation partitioning analysis (VPA). The results indicated that GCG (gallocatechin gallate), EGCG (epigallocatechin gallate) and GA as well as the interactions among them were the most probably ones to influence, or be influenced by the fungal communities during the fermentation process of Fu brick tea. This study revealed fungal succession, metabolite changes and their relationships, provided new insights into the mechanisms for manufacturing process of Fu brick tea.

In tea (Camellia sinensis) plants, polyphenols are the representative metabolites and play important roles during their growth. Among tea polyphenols, catechins are extensively studied, while very little attention has been paid to other polyphenols such as gallic acid (GA) that occur in tea leaves with relatively high content. In this study, GA was able to be transformed into methyl gallate (MG), suggesting that GA is not only a precursor of catechins, but also can be transformed into other metabolites in tea plants. GA content in tea leaves was higher than MG content—regardless of the cultivar, plucking month or leaf position. These two metabolites occurred with higher amounts in tender leaves. Using nonaqueous fractionation techniques, it was found that GA and MG were abundantly accumulated in peroxisome. In addition, GA and MG were found to have strong antifungal activity against two main tea plant diseases, Colletotrichum camelliae and Pseudopestalotiopsis camelliae-sinensis. The information will advance our understanding on formation and biologic functions of polyphenols in tea plants and also provide a good reference for studying in vivo occurrence of specialized metabolites in economic plants.

Syringic acid (SA), a phenolic compound, is found naturally in several plants, fruits, and vegetables and has numerous therapeutic attributes. The objective of the research was to investigate the possible impact of syringic acid nanoparticles (SANPs) on hyperglycemia, particularly in relation to advanced glycation end products, reactive oxygen species, and inflammation. SANPs were prepared by ionic gelation method and characterized. Rats were divided into 5 groups, normal control, high-fat and high-fructose diet (HFFD), HFFD + metformin (120 mg/kg), HFFD + SA (30 mg/kg) and HFFD + SANPs (15 mg/kg). Rats showed a remarkable decrease in body weight (↓31.61%) and fasting blood glucose levels (↓62.63%) in HFFD + SANPs group. The HbA1c decreased from 5.8 ± 0.05% in HFFD to 4.4 ± 0.12% in HFFD + SA and 4.1 ± 0.16% in HFFD + SANPs treatment groups. The administration of SANPs resulted in a considerable improvement ( p  < 0.001) in the activity of glyoxalase-1 (Glo1, 0.19 ± 0.003 U/mg protein), glyoxalase-2 (Glo2, 0.14 ± 0.002 U/mg protein) and hexokinase-2 (29.19 ± 2.24 ng/dL). There was a significant decrease ( p  < 0.001) in malondialdehyde (MDA) levels along with increased glutathione (GSH), superoxide-dismutase (SOD) and catalase activity. The in-silico analysis indicated potential binding affinities with hexokinase 2 (-5.4), IL-6 (-5.7), catalase (-5.8), MDA (-5.4) and GSH (-5.1). Furthermore, these interventions resulted in enhancements in the plasma concentrations of lipid profile components as well as improvements in liver function tests and expression of pro-inflammatory cytokines including IL-6, IL-8 and NF-κB. Utilization of SANPs holds promise as a therapeutic strategy for mitigating hyperglycemia.

Paraquat (PRQ) is a toxic chemical compound that is very noxious to animals and humans. Gallic acid is a phenolic compound that has antioxidant properties. In this study, we evaluated the ameliorative effect of gallic acid against PRQ-induced renal injury and oxidative stress. In this research, the rats were segregated into six groups. Group 1 is the control group; group 2 received paraquat only; group 3 received gallic acid only; and groups 4, 5, and 6 received paraquat plus gallic acid at doses of 25, 50, and 100 mg/kg bw respectively. Findings of this work displayed that the renal contents of the vitamin C, superoxide dismutase (SOD), and catalase (CAT) significantly reduced and the levels of the serum protein carbonyl, creatinine, serum glutamate pyruvate transaminase (sGPT), urea, serum glutamate oxaloacetate transaminase (sGOT), uric acid, MDA, serum IL-1β, and the kidney IL-1β gene expression were remarkably increased in the group receiving PRQ only compared with that in the control group. On the other hand, treatment with gallic acid after exposure to PRQ led to a significant elevation in renal vitamin C, SOD, and CAT levels plus a remarkable decrease in the serum protein carbonyl, creatinine, sGPT, urea, sGOT, uric acid, MDA, IL-1β, and renal gene expression of IL-1β in comparison with the PRQ-only-treated rats. Histological changes were also ameliorated by gallic acid administration. The data approve that gallic acid diminished the deleterious effects of PRQ exposure. In this regard, our results indicated that the administration of gallic acid could alleviate the noxious effects of PRQ on the antioxidant defense system and renal tissue.

Gallic acid (GA), a plant-derived ubiquitous secondary polyphenol metabolite, can be a useful dietary supplement. This in vitro study’s primary purpose was to assess the anti-aging properties of GA using rat embryonic fibroblast (REF) cells, antidiabetic effects via pancreatic islet cells, and finally, elucidating the molecular mechanisms of this natural compound. REF and islet cells were isolated from fetuses and pancreas of rats, respectively. Then, several senescence-associated molecular and biochemical parameters, along with antidiabetic markers, were investigated. GA caused a significant decrease in the β-galactosidase activity and reduced inflammatory cytokines and oxidative stress markers in REF cells. GA reduced the G0/G1 phase in senescent REF cells that led cells to G2/M. Besides, GA improved the function of the β cells. Flow cytometry and spectrophotometric analysis showed that it reduces apoptosis via inhibiting caspase-9 activity. Taken together, based on the present findings, this polyphenol metabolite at low doses regulates different pathways of senescence and diabetes through its antioxidative stress potential and modulation of mitochondrial complexes activities.