Gallic acid (GA) has been found by a large number of studies to have pharmacological effects such as antioxidant and anti-inflammatory properties. However, the underlying therapeutic mechanisms are not fully understood.. Studies have shown that altering the intestinal flora affects host metabolism and effectively mediates the development of synovitis. The aim of this study was to explore the pharmacological effects of GA in the treatment of synovial inflammation and anti-synovial fibrosis in knee osteoarthritis (KOA) and the underlying mechanisms by macrogenomics combined with off-target metabolomics. We established a synovitis model via in vivo and in vitro experiments to observe the effect of GA intervention on synovitis. Moreover, we collected serum and feces from rats and analyzed the changes in intestinal flora by macro-genome sequencing and the changes in metabolites in the serum by untargeted metabolomics. We found that GA reduced the levels of IL-1β, IL-6, and TNF-α, and decreased the protein expression levels of α-SMA, TGF-β, and Collagen I in synovial tissues and cells, and the composition and function of the intestinal flora were similarly altered. Combined with macrogenomic pathway enrichment analysis and metabolic pathway enrichment analysis, these findings revealed that GA impacts Bacteroidia and Muribaculaceae abundance, and via the following metabolic pathways: sphingolipid metabolism, glycerophospholipid metabolism, and arginine biology.to ameliorate synovial inflammation and fibrosis in KOA. The therapeutic effect of GA on KOA synovitis and fibrosis is partly attributed to the alleviation of metabolic disorder and the rebalancing of the intestinal flora. These results provides a rationale for the therapeutic application of GA in the treatment of synovitis.

Antibiotic resistance has increased in recent years, especially for pathogens like Klebsiella pneumoniae. Discovering and developing new drugs is challenging due to the high resistance of pathogens. Metal nanoparticles have been widely used in recent years to overcome and treat infections. Gallic acid-coated iron oxide nanoparticles (IONPs-GA) were synthesized in a simple and cost-effective method. The morphology characteristics of synthesized IONPs-GA were analyzed using Fourier transform infrared spectroscopy (FTIR), x-ray diffraction analysis (XRD), and scanning electron microscope (SEM) analysis. IONPs were mostly spherical in shape with sizes ranging between 32 and 61 nm. All analyses used in this study confirmed the successful coating of gallic acid to iron oxide. Biological activities were studied phenotypically and on the molecular level, including antibacterial, antibiofilm, and mRNA levels of capsule-associated genes. The results showed high antimicrobial activity of the synthesized nanoparticles against different G+ve and G-ve bacteria. The highest activity was recorded against Staphylococcus aureus (43 mm) and K. pneumoniae (22 mm). The MIC of IONPs against K. pneumoniae was 3.12 mg/mL and SEM analysis showed adhering the IONPs-GA to the cell surface of K. pneumoniae resulted in disrupting the cell membrane. Different concentrations of sub-MIC inhibited K. pneumoniae biofilm formation with the highest inhibition percentage at ½ × MIC (66.86%). Also, the synthesized IONPs-GA differently affected the regulation and mRNA level of capsule-associated genes in K. pneumoniae. The results indicated that IONPs-GA could be useful in biological applications such as in drug delivery and treatment wide range of pathogens. RESEARCH HIGHLIGHTS: Gallic acid was successfully coated into iron oxide nanoparticles synthesized in a simple way. IONPs-GA was morphologically characterized using FTIR, XRD, and SEM. Evaluation the activity of IONPs-GA as antibacterial, antibiofilm, and study the potential level of mRNA affected by IONPs-GA.

Developing T1-weighted magnetic resonance imaging (MRI) contrast agents with enhanced biocompatibility and targeting capabilities is crucial owing to concerns over current agents\' potential toxicity and suboptimal performance. Drawing inspiration from \"biomimetic camouflage,\" we isolated cell membranes (CMs) from human glioblastoma (T98G) cell lines via the extrusion method to facilitate homotypic glioma targeting. At an 8:1 mass ratio of ferric chloride hexahydrate to gallic acid (GA), the resulting iron (Fe)-GA nanoparticles (NPs) proved effective as a T1-weighted MRI contrast agent. T98G CM-coated Fe-GA NPs demonstrated improved homotypic glioma targeting, validated through Prussian blue staining and in vitro MRI. This biomimetic camouflage strategy holds promise for the development of targeted theranostic agents in a safe and effective manner.

To improve the color stability of anthocyanins (ACNs) in blueberry fermented beverage, the intermolecular copigmentation between ACNs and 3 different phenolic compounds, including (-)-epigallocatechin gallate (EGCG), ferulic acid (FA), and gallic acid (GA) as copigments, was compared in the model and the real blueberry fermented beverage, respectively. The copigmented ACNs by EGCG presented a high absorbance (0.34 a.u.) and redness (27.09 ± 0.17) in the model blueberry fermented beverage. The copigmentation by the participation of the 3 different phenolic compounds showed all a spontaneous exothermic reaction, and the Gibbs free energy (ΔG°) of the system was lowest (-5.90 kJ/mol) using EGCG as copigment. Furthermore, the molecular docking model verified that binary complexes formed between ACNs and copigments by hydrogen bonds and π-π stacking. There was a high absorbance (1.02 a.u.), percentage polymeric color (PC%, 68.3 %), and good color saturation (C*ab, 43.28) in the real blueberry fermented beverage aged for 90 days, and more malvidin-3-O-glucoside had been preserved in the wine using EGCG as copigment. This finding may guide future industrial production of blueberry fermented beverage with improved color.

To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100 male SD rats were randomly divided into four groups: normal control group, simple high IOP group, 0.5% gallic acid experimental group, and 1% gallic acid experimental group. HE staining, immunofluorescence, DHE staining, Western blot, and q-PCR were used to observe the antioxidant effect of gallic acid on the retina of acute ocular hypertension rats. HE staining of the retina of SD rats confirmed that the nucleus of RGCs was clear, the thickness of the RNFL was regular in the normal control group, and the nucleus of RGCs was ruptured and lysed in the simple high intraocular pressure (IOP) group and the gallic acid group, and the thickness of the RNFL was significantly thickened, but the thickness of the RNFL in the gallic acid group was significantly reduced compared with that in the simple high IOP group (p < 0.05). DHE staining showed that ROS content in the simple high IOP group was significantly increased compared with the normal control group, and ROS content was significantly decreased after the application of gallic acid (p < 0.05). Immunofluorescence staining with Brn-3a antibody confirmed that the number of RGCs was significantly reduced in the simple high IOP group compared with the normal control group, whereas after application of gallic acid, the number of RGCs was significantly more in the gallic acid group than in the simple high IOP group (p < 0.05). Western Blot and q-PCR confirmed that hypoxia-inducing factor 1α (HIF-1α) protein content and transcription level were significantly increased in the retinal tissue of the simple high IOP group, and gallic acid could inhibit HIF-1α protein content (p < 0.05) and reduce transcription factor level (p < 0.05). Gallic acid exerts a protective effect on RGC by inhibiting oxidative stress in rats with acute IOP elevation.

Chitosan (CS)-based photo-cross-linkable hydrogels have gained increasing attention in biomedical applications. In this study, we grafted CS with gallic acid (GA) by carbodiimide chemistry to prepare the GA-CS conjugate, which was subsequently modified with methacrylic anhydride (MA) modification to obtain the methacrylated GA-CS conjugate (GA-CS-MA). Our results demonstrated that the GA-CS-MA hydrogel not only exhibited improved physicochemical properties but also showed antibacterial, antioxidative, and anti-inflammatory capacity. It showed moderate antibacterial activity and especially showed a more powerful inhibitory effect against Gram-positive bacteria. It modulated macrophage polarization, downregulated pro-inflammatory gene expression, upregulated anti-inflammatory gene expression, and significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) production under lipopolysaccharide (LPS) stimulation. Subcutaneously implanted GA-CS-MA hydrogels induced significantly lower inflammatory responses, as evidenced by less inflammatory cell infiltration, thinner fibrous capsule, and predominately promoted M2 polarization. This study provides a feasible strategy to prepare CS-based photo-cross-linkable hydrogels with improved physicochemical properties for biomedical applications.

Specific anthocyanins and phenolic compounds exhibit acetylcholinesterase inhibitory (AChEi) activity. In this study, the AChEi activity of jaboticaba peel extracts were investigated based on their high phenol contents. Jaboticaba peel ethanolic extract (PEX) and aqueous extract (PAX) were prepared by extracting jaboticaba peel with 95% ethanol and boiling water, respectively. Through HPLC-MS/MS and HPLC-PDA analysis, gallic acid was identified in PAX with a concentration of 598.13 ± 42.43 mg/100 g extract, and ellagic acid in PEX with a concentration of 350.47 ± 8.53 mg/100 g extract. Both PEX and PAX showed dose-dependent inhibition against AChE activity, with IC50 values of 3.54 and 4.07 mg/mL, respectively. The mechanism of inhibition of PEX was determined to be non-competitive inhibition based on the decreasing V max and relatively constant K m with increasing PEX concentration, as determined using a Lineweaver-Burk plot.

Rice bean [Vigna umbellata (Thunb.) Ohwi and Ohashi], an annual legume in the genus Vigna, is a promising crop suitable for cultivation in a changing climate to ensure food security. It is also a medicinal plant widely used in traditional Chinese medicine; however, little is known about the medicinal compounds in rice bean. In this study, we assessed the diuretic effect of rice bean extracts on mice as well as its relationship with the contents of eight secondary metabolites in seeds. Mice gavaged with rice bean extracts from yellow and black seeds had higher urinary output (5.44-5.47 g) and water intake (5.8-6.3 g) values than mice gavaged with rice bean extracts from red seeds. Correlation analyses revealed significant negative correlations between urine output and gallic acid (R = -0.70) and genistein (R = -0.75) concentrations, suggesting that these two polyphenols negatively regulate diuresis. There were no obvious relationships between mice diuresis-related indices (urine output, water intake, and weight loss) and rutin or catechin contents, although the concentrations of both of these polyphenols in rice bean seeds were higher than the concentrations of the other six secondary metabolites. Our study findings may be useful for future research on the diuretic effects of rice bean, but they should be confirmed on the basis of systematic medical trials.

Microcystis aeruginosa is the main toxic strain in cyanobacterial blooms, and the recruitment stage in its temperature-dependent seasonal succession is considered as the key to its subsequent growth. In this study, a protocol with specific temperature settings was developed as the simulated recruitment stage in order to investigate and confirm the superior inhibitory effects of allelochemicals on M. aeruginosa at that stage of recruitment. One of the most common allelochemicals, gallic acid (GA) (10 mg/L, 20 mg/L) was employed to treat M. aeruginosa under initially low temperature condition (15 °C), then intermediate (20 °C) and last normal (26 °C), which corresponds to the critical temperatures for cyanobacterial recruitment and growth. Growth, metabolism, photosynthetic activity, extracellular polysaccharides (EPS) and microcystins (MCs) release were analyzed and discussed in this study, and a more sustained and better inhibitory effect over a 20-day period was achieved. Notably, GA (10 mg/L) markedly delayed the recruitment of M. aeruginosa from low temperature, with an inhibition efficiency of 85.71 %, and suppressing Fv/Fm and photosynthetic pigments production. It is also observed that M. aeruginosa at recruitment stage exhibited higher sensitivity and poorer resistance to allelochemical treatment, with variable responses suggesting that optimal dosages may alter. The antioxidant enzyme activities remained high under prolonged stress, and the secretion of EPS was stimulated, indicating that cyanobacteria were more inclined to form colonies. While the laboratory-based inhibitory mechanism appeared to increase the release of microcystins in individual cells, the actual concentration of microcystins in natural aquatic environments requires further investigation.

The unique \"Iron Addiction\" feature of cancer stem cells (CSCs) with tumorigenicity and plasticity generally contributes to the tumor recurrence and metastasis after a lumpectomy. Herein, a novel \"Ferroptosis Amplification\" strategy is developed based on integrating gallic acid-modified FeOOH (GFP) and gallocyanine into Pluronic F-127 (F127) and carboxylated chitosan (CC)-based hydrogel for CSCs eradication. This \"Ferroptosis Amplifier\" hydrogel is thermally sensitive and achieves rapid gelation at the postsurgical wound in a breast tumor model. Specifically, gallocyanine, as the Dickkopf-1 (DKK1) inhibitor, can decrease the expression of SLC7A11 and GPX4 and synergistically induce ferroptosis of CSCs with GFP. Encouragingly, it is found that this combination suppresses the migratory and invasive capability of cancer cells via the downregulation of matrix metalloproteinase 7 (MMP7). The in vivo results further confirm that this \"Ferroptosis Amplification\" strategy is efficient in preventing tumor relapse and lung metastasis, manifesting an effective and promising postsurgical treatment for breast cancer.