Broad-Spectrum Antibacterial Activity of Antioxidant Octyl Gallate and Its Impact on Gut Microbiome.

In this study, we investigated the antibacterial activity of octyl gallate (OG), an antioxidant food additive, against both Gram-positive and Gram-negative bacterial pathogens. OG demonstrated robust bactericidal activity against Gram-positive bacterial pathogens with minimum inhibitory concentrations (MIC) of 4 to 8 µg/mL and minimum bactericidal concentrations (MBC) of 8 to 16 µg/mL in vitro. However, OG exhibited limited antibacterial activity against Gram-negative bacteria, including E. coli, although it could inhibit bacterial growth in vitro. Importantly, OG administration in mice altered the fecal microbiome, significantly reducing microbial diversity, modifying community structure, and increasing the abundance of beneficial bacteria. Additionally, OG displayed low cytotoxicity and hemolytic activity. These findings suggest that OG could be developed as a novel antibacterial agent, particularly against multi-drug-resistant MRSA. Our results provide new insights into the therapeutic potential of OG in modulating the gut microbiome, especially in conditions associated with microbial imbalance, while ensuring food safety.

Identification of octyl gallate, a novel apoptosis-inducing compound for colon cancer therapy, from Sanguisorba officinalis L. by cell membrane chromatography and UHPLC-(Q)TOF-MS/MS.

Colon cancer is a common gastrointestinal malignancy that ranks third in incidence among gastrointestinal cancers. Therefore, screening bioactive compounds for treatment of colon cancer is urgently needed. Sanguisorba officinalis L. (SO) has been demonstrated that the extractions or monomers possess potential anti-tumor effect. In this study, we firstly used cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled with (quadrupole) time-of-flight mass spectrometry (UHPLC-(Q) TOF-MS/MS) to identify a novel active ingredient, octyl gallate (OG), from SO methanol extract (SO-MtOH). HCT116 and SW620 cells lines were used for in vitro research, which showed OG presents great anti-colon cancer effect by inhibiting proliferation, inducing apoptosis, and repressing the migration and invasion. Furthermore, SW620 bearing athymic nude mice was used to investigate the potential antitumor activity in vivo, which exhibited OG treatment remarkably lessened the tumor volume. Mechanism studies showed that OG downregulated the PI3K/AKT/mTOR signaling axis and induced apoptosis by upregulating the Bax/Bcl-2 protein and the cleaved caspase-3, caspase-9. In conclusion, our research innovatively applied the method of CMC to intriguingly unearth the potential anti-colon cancer ingredient OG and demonstrated its the great antineoplastic activity, which provide a new insight for researchers efficiently developing the novel apoptosis-inducing compound for colon cancer therapy.

Targeted inhibition of gut bacterial ß-glucuronidases by octyl gallate alleviates mycophenolate mofetil-induced gastrointestinal toxicity.

Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated ß-glucuronidase (ßGUS). Therefore, controlling microbiota-produced ßGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation. In this study, the octyl gallate (OG) was identified with promising inhibitory activity on hydrolysis of PNPG in our high throughput screening based on a chemical collection of approximately 2000 natural products. Furthermore, OG was also found to inhibit a broad spectrum of BGUSs, including mini-Loop1, Loop 2, mini-Loop 2, and mini-Loop1,2. The further in vivo experiments demonstrated that administration of 20 mg/kg OG resulted in predominant reduction in the activity of BGUSs while displayed no impact on the overall fecal microbiome in mice. Furthermore, in the MMF-induced colitis model, the administration of OG at a dosage of 20 mg/kg effectively mitigated the gastrointestinal toxicity, and systematically reverted the colitis phenotypes. These findings indicate that the OG holds promising clinical potential for the prevention of MMF-induced gastrointestinal toxicity by inhibition of BGUSs and could be developed as a combinatorial therapy with MFF for better clinical outcomes.

Octyl gallate has potent anti-inflammasome activity by directly binding to NLRP3 LRR domain.

The NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome plays key roles in regulating inflammation. Numerous studies show that the abnormal activation of NLRP3 associates with the initiation and progression of various diseases. Hence, the NLRP3 inflammasome may be a promising therapeutic target for these diseases. Octyl gallate (OG) is a small molecule with antioxidant, antimicrobial, antifungal, and anti-inflammatory activities; however, the mechanism underlying its anti-inflammatory activity is still unclear. Here, we developed a screening system for NLRP3-inflammasome inhibitors. A total of 3287 small molecules were screened for inhibitors of nigericin-induced NLRP3 oligomerization. OG was identified as a novel inhibitor. We show that OG directly targets the LRR domain of NLRP3 and thereby blocks the inflammatory cascade of the NLRP3 inflammasome. This contrasts with the mode-of-action of other direct NLRP3 inhibitors, which all bind to the NACHT domain of NLRP3. Interestingly, OG also inhibits the priming step by downregulating the Raf-MEK1/2-ERK1/2 axis. Thus, OG inhibits the NLRP3 inflammasome by two distinct mechanisms. Importantly, OG injection ameliorated the inflammation in mouse models of foot gout and sepsis. Our study identifies OG as a potential therapeutic agent for NLRP3-associated diseases.

Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV.

Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel antiviral drug against PEDV. The OG exhibited a potential broad-spectrum antiviral drug for control of other swine enteric coronaviruses.

Food additive octyl gallate eliminates acrolein and inhibits bacterial growth in oil-rich food.

Acrolein (ACR) is predominantly generated from oil-rich food during thermos- processing. Accumulation of ACR in vivo through food consumption has been associated with an increased risk of developing chronic diseases. Here, we investigated the inhibitory effect of octyl gallate (OG), a new food additive tolerant to high-temperature, alkaline and fat-soluble saturations, on the generation of ACR in OG-ACR, oil-Rancimat models, and real-world frying. Our results demonstrate that approximately 80% and 60% of ACR was eliminated by OG in the two models, respectively, and OG-ACR was detected in the deep-frying process using LC-MS/MS. The reaction pathways were clarified by synthesis and OG-ACR and OG-2ACR adduct structural elucidation. Our work reveals that the antibacterial activity of OG-ACR against Escherichia coli (gram-negative) was four times higher than that of OG. Thus, OG can be developed as a promising novel ACR scavenger for high-temperature food processing and an antibacterial agent in food storage.

Dual-Stage Blue-Light-Guided Membrane and DNA-Targeted Photodynamic Inactivation Using Octyl Gallate for Ultraefficient Eradication of Planktonic Bacteria and Sessile Biofilms.

This study aimed to investigate the synergistic bactericidal activity and mechanism of dual-stage light-guided membrane and DNA-targeted photodynamic inactivation (PDI) by the combination of blue light (BL, 420 nm) and the food additive octyl gallate (OG) against Vibrio parahaemolyticus in planktonic and biofilm growth modes. While OG serves as an outstanding exogenous photosensitizer, the planktonic cells were not visibly detectable after the OG-mediated PDI treatment with 0.2 mM OG within 15 min (191.7 J/cm2), and its biofilm was nearly eradicated within 60 min (383.4 J/cm2). Gram-positive Staphylococcus aureus was more susceptible to the PDI than Gram-negative V. parahaemolyticus. The cellular wall and proteins, as well as DNA, were the vulnerable targets for PDI. The membrane integrity could be initially disrupted by OG bearing a hydrophilic head and a hydrophobic tail via transmembrane insertion. The enhancement of OG uptake due to the first-stage light-assisted photochemical internalization (PCI) promoted the accumulation of OG in cells. It further boosted the second-stage light irradiation of the photosensitizer-inducing massive cell death. Upon the second-stage BL irradiation, reactive oxygen species (ROS) generated through the OG-mediated PDI in situ could extensively deconstruct membranes, proteins, and DNA, as well as biofilms, while OG could be activated by BL to carry out photochemical reactions involving the formation of OG-bacterial membrane protein (BMP) covalent conjugates and the interactions with DNA. This dual-stage light-guided subcellular dual-targeted PDI strategy exhibits encouraging effects on the eradication of planktonic bacteria and sessile biofilms, which provides a new insight into the development of an ultraeffective antimicrobial and biofilm removing/reducing technique to improve microbiological safety in the food industry.

Investigation of Antiparasitic Activity of Two Marine Natural Products, Estradiol Benzoate, and Octyl Gallate, on Toxoplasma gondii In Vitro.

Toxoplasmosis, caused by Toxoplasma gondii, is a common disease worldwide and could be severe and even fatal in immunocompromised individuals and fetuses. Limitation in current available treatment options drives the need to develop novel therapeutics. This study assessed the anti-T. gondii potential of 103 marine natural products. A luminescence-based ß-galactosidase activity assay was used to screen the marine natural products library. Afterward, those compounds that displayed over 70% parasite inhibition ratio were further chosen to assess their cytotoxicity. Compounds exhibiting low cytotoxicity (≥80% cell viability) were applied to evaluate the inhibition efficacy on discrete steps of the T. gondii lytic cycle, including invasion, intracellular growth, and egress abilities as well as the cell cycle. We found that both estradiol benzoate and octyl gallate caused >70% inhibition of tachyzoite growth with IC50 values of 4.41 ± 0.94 and 5.66 ± 0.35 µM, respectively, and displayed low cytotoxicity with TD50 values of 34.11 ± 2.86 and 26.4 ± 0.98 µM, respectively. Despite their defects in inhibition of invasion and egress of tachyzoite, the two compounds markedly inhibited the tachyzoite intracellular replication. Flow cytometric analyses further suggested that the anti-T. gondii activity of estradiol benzoate, rather than octyl gallate, may be linked to halting cell cycle progression of tachyzoite from G1 to S phase. Taken together, these findings suggest that both estradiol benzoate and octyl gallate are potential inhibitors for anti-T. gondii infection and support the further exploration of marine natural products as a thinkable source of alternative and active agents against T. gondii.

Octyl gallate decrease lymphocyte activation and regulates neutrophil extracellular traps release.

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.

New Horizons in Microbiological Food Safety: Ultraefficient Photodynamic Inactivation Based on a Gallic Acid Derivative and UV-A Light and Its Application with Electrospun Cyclodextrin Nanofibers.

An excellent bactericidal effect of octyl gallate (OG)-mediated photodynamic inactivation (PDI) against foodborne pathogens (Escherichia coli and Staphylococcus aureus) was evaluated in relation to the mode of action. UV-A irradiation (wavelength, 365 nm; irradiance, 8.254 ± 0.18 mW/cm2) of the bacterial suspension containing 0.15 mM OG could lead to a >5-log reduction of viable cell counts within 30 min for E. coli and only 5 min for S. aureus. Reactive oxygen species (ROS) formation was considered the main reason for the bactericidal effect of OG + UV-A light treatment because toxic ROS induced by OG-mediated PDI could attack the cellular wall, proteins, and DNA of microbes. Moreover, the bactericidal effect, as well as the yields of ROS, depended on OG concentrations, irradiation time, and laser output power. Furthermore, we prepared an edible photodynamic antimicrobial membrane comprising electrospun cyclodextrin nanofibers (NFs) by embedding OG. The resultant OG/HPßCD NFs (273.6 µg/mL) under UV-A irradiation for 30 min (14.58 J/cm) could cause a great reduction (>5-log) of viable bacterial counts of E. coli. The in situ photodynamic antibacterial activity of OG/HPßCD NF-based packaging was evaluated during the Chinese giant salamander storage. Overall, this research highlights the dual functionalities (antibacterial and photodynamic properties) of OG as both an antibacterial agent and photosensitizer and the effectiveness of electrospun NFs containing OG as an active antibacterial packaging material for food preservation upon UV light illumination.

Proteomics Reveals Octyl Gallate as an Environmentally Friendly Wood Preservative Leading to Reactive Oxygen Species-Driven Metabolic Inflexibility and Growth Inhibition in White-Rot Fungi (Lenzites betulina and Trametes versicolor).

The most commonly applied wood preservatives are based on creosote, pentachlorophenol, and waterborne chromate copper arsenate, which negatively affect the environment. Thus, environmentally friendly wood preservatives are required. This study investigated the antifungal activity and mechanism of several long-chain alkyl gallates (3,4,5-trihydroxybenzoates) against white-rot fungi, Lenzites betulina and Trametes versicolor. The results revealed that octyl gallate (OG) had the best antifungal activity. Additionally, OG may have a mechanism of action similar to surfactants and inhibit ATPase activity, causing mitochondrial dysfunction and endogenous reactive oxygen species (ROS) production. Upon exposure to endogenous ROS, cells rapidly inhibit the synthesis of 60S ribosomal subunits, thus reducing the mycelial growth rate. L. betulina and T. versicolor also remodeled their energy metabolism in response to low ATP levels and endogenous ROS. After OG treatment, ATP citrate synthase activity was downregulated and glycolytic activity was upregulated in L. betulina. However, the activity of aerobic pathways was decreased and the oxidative branch of the pentose phosphate pathway was redirected form nicotinamide adenine dinucleotide phosphate (NADPH) to minimize endogenous ROS-mediated damage in T. versicolor. Taken together, these observations reveal that OG is a potent inhibitor of white-rot fungus. Further structural optimization research and pharmacological investigations are warranted.

Octyl gallate induces hepatic steatosis in HepG2 cells through the regulation of SREBP-1c and PPAR-gamma gene expression.

Octyl gallate (OG) is an antioxidant commonly used in food, although there is no definition of its acceptable daily intake. There are reports in vitro and in vivo showing that food additives and drugs can alter lipid metabolism. Lipid droplet accumulation in hepatic cells is one of the main findings in the unregulated lipid metabolism and is strongly related to the development of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of OG on lipid metabolism in the hepatocellular carcinoma cell line (HepG2). The results have shown, for the first time, that treatment with OG increased the overall amount of lipids, the triglyceride concentration, the lipid droplet area, and SREBP-1c and PPAR-γ gene expression. Taken together, the findings indicate that OG induces lipid droplet accumulation in HepG2 cells through the regulation of SREBP-1c and PPAR-γ gene expression without involving mTOR/S6K1 and may contribute to NAFLD when used as a food additive.

The Anti-Inflammatory Effect of Octyl Gallate Through Inhibition of Nuclear Factor-κB (NF-κB) Pathway in Rat Endometriosis Model.

BACKGROUND: Endometriosis is a chronic inflammatory condition associated with an increased risk of epithelial ovarian cancer. Our previous studies found that the anti-inflammatory effect of octyl gallate in endometriosis cell culture was more effective than gallic acid and heptyl gallate. This study aimed to analyze the anti-inflammatory effect of octyl gallate in rat endometriosis model. METHODS: Thirty female Wistar rats were randomly divided into three groups. Group I was the sham-operated group, group II was the surgically-induced endometriosis group, whereas group III was the surgically-induced endometriosis group and each rat was administered with 20 mg of octyl gallate dissolved in 1 ml Na-CMC via oral gavage once a day for 30 days. When all rats were euthanized, the endometrial tissue from group I and last two groups were collected for further analysis. TNF-α levels were measured using Luminex, while non-phosphorylated NF-κB and COX-2 levels were analyzed using ELISA. RESULTS: The average of non-phosphorylated NF-κB levels in group III (4.970±0.971 pg/mgP) was significantly higher than group II (3.97±0.656 pg/mgP). Moreover, the proportion of rats with the high level of non-phosphorylated NF-κB in group III was 45.6% higher than group II (p<0.05). The proportion of rats with the high level of COX-2 in group III was 22.3% lower than group II (p<0.05). However, there was no significant difference in TNF-α levels between all groups. CONCLUSION: The anti-inflammatory effect of octyl gallate may has effects in NF-κB activation and reduction of COX-2 levels in rat endometriosis model.

Octyl gallate reduces ABC multidrug transporter CaCdr1p expression and leads to its mislocalisation in azole-resistant clinical isolates of Candida albicans.

OBJECTIVES: Fungal pathogens pose a serious threat to public health. Widespread and prolonged use of antifungal drugs has led to the development of multidrug resistance in the human fungal pathogen Candida albicans. Among several mechanisms leading to drug resistance in C. albicans, overexpression of drug efflux transporters remains by far the leading cause of multidrug resistance, facilitated by overexpression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporters. Hence, targeting efflux pumps still represents a promising approach to combat multidrug resistance. In this study, the effect of octyl gallate (OG), a natural food additive, on drug efflux pump activity of C. albicans was analysed. METHODS: Drug efflux pump activity was determined by rhodamine 6G (R6G) efflux and Nile red accumulation assay in a Candida drug resistance protein 1 (CaCdr1p)-overexpressing strain. Gene expression and protein expression and localisation were studied by RT-PCR, Western blot and confocal microscopy. Ergosterol content was measured by the alcoholic KOH method. RESULTS: OG specifically inhibits the activity of CaCdr1p, belonging to the ABC superfamily. The underlying mechanism was confirmed as competitive mode of inhibition by OG as revealed by Lineweaver-Burk plot. Furthermore, OG leads to reduced expression of CDR1 and CaCdr1p and mislocalisation of CaCdr1p. Additionally, OG sensitises azole-susceptible and -resistant clinical matched-pair isolates Gu4 & Gu5 and leads to impeded R6G efflux and depleted ergosterol content. CONCLUSION: The ability of OG as a potent inhibitor of CaCdr1p that chemosensitises drug-resistant C. albicans warrants further studies to be exploited as an effective antifungal agent.

Entropy-driven binding of octyl gallate in albumin: Failure in the application of temperature effect to distinguish dynamic and static fluorescence quenching.

Fluorescence quenching is widely used to obtain association constants between proteins and ligands. This methodology is based on assumption that ground-state complex between protein and ligand is responsible for quenching. Here, we call the attention about the risk of using the temperature criterion for decision of applying or not fluorescence quenching data to measure association constants. We demonstrated that hydrophobic effect can be the major force involved in the interaction and, as such, superposes the well-established rationalization that host/guest complexation is weakened at higher temperatures due to loss of translational and rotational degrees of freedom. To do so, the complexation of bovine serum albumin with octyl gallate was studied by steady-state, time-resolved fluorescence spectroscopy and isothermal titration calorimetry. The results clearly demonstrated the complexation, even though the Stern-Volmer constant increased at higher temperatures (1.6 × 104 and 4.1 × 105 mol-1 L at 20°C and 40°C), which could suggest a simple dynamic process and not complexation. The entropy-driven feature of the interaction was demonstrated by the unfavorable enthalpy (∆H° = 104.4 kJmol-1 ) but favorable entropy (∆S° = 447.5 Jmol-1 K-1 ). The relevance of the ligand hydrophobicity was also evaluated by comparing ascorbic acid and its ester ascorbyl palmitate. Docking simulations showed a higher number of hydrophobic contacts and lower energy poses for the esters, confirming the experimental results. In conclusion, the well-established rationalization that host/guest complexation is weakened at higher temperatures is not straightforward for protein-ligand interactions. Hence, the temperature effect for a decision between static and dynamic quenching and its use to decide if a complexation at ground state is taking place between ligand and protein should not be used.

Anti-inflammatory effect of octyl gallate in alveolar macrophages cells and mice with acute lung injury.

Acute lung injury (ALI) is an inflammatory process, and has high incidence and mortality. ALI and the acute respiratory distress syndrome are two common complications worldwide that result in acute lung failure, sepsis, and death. Pro-inflammatory substances, such as cytokines and chemokines, are responsible for activating the body's defense mechanisms and usually mediate inflammatory processes. Therefore, the research of substances that decrease the uncontrolled response of organism is seen as potential for patients with ALI. Octyl gallate (OG) is a phenolic compound with therapeutic actions namely antimicrobial, antiviral, and antifungal. In this study, we evaluated its action on lipopolysaccharide (LPS)-activated alveolar macrophages RAW 264.7 cells and ALI in male mice. Our results demonstrated protective effects of OG in alveolar macrophages activated with LPS and mice with ALI. The OG treatment significantly decreased the inflammatory markers in both studies in vitro and in vivo. The data suggested that OG can act as an anti-inflammatory agent for ALI.

Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression.

The accumulation of biofilm by Streptococcus mutans bacteria on hard tooth tissues leads to dental caries, which remains one of the most prevalent oral diseases. Hence, the development of new antibiofilm agents is of critical importance. The current study reports the results from testing the effectiveness of octyl gallate (C8-OG) against: (1) S. mutans biofilm formation on solid surfaces (polystyrene, glass), (2) acidogenicity, (3) and the expression of biofilm-related genes. The amount of biofilm formed by S. mutans bacteria was evaluated using the colorimetric method and optical profilometry. The pH of the biofilm growth medium was measured with microelectrode. A quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the expression of genes encoding glucan binding protein B (gbpB), glucosyltransferases B, -C, -D (gtfB, -C, -D), and the F-ATPase ß subunit of the F1 protein (atpD). The results show that C8-OG significantly diminished biofilm formation by exposed S. mutans on solid surfaces and suppressed acidogenicity in a dose-dependent manner, compared to unexposed bacteria (p < 0.05). The C8-OG concentration of 100.24 µM inhibited S. mutans biofilm development on solid surfaces by 100% and prevented a decrease in pH levels by 99%. In addition, the RT-qPCR data demonstrate that the biofilm-producing bacteria treated with C8-OG underwent a significant reduction in gene expression in the case of the four genes under study (gbpB, gtfC, gtfD, and atpD), and there was a slight decrease in expression of the gtfB gene. However, C8-OG treatments did not produce significant expression change compared to the control for the planktonic cells, although there was a significant increase for the atpD gene. Therefore, C8-OG might be a potent antibiofilm and/or anticaries agent for oral formulations that aim to reduce the prevalence of dental caries.

Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth.

Octyl gallate (OG) is a common antioxidant and preservative safely used in food additive and cosmetics. In this study, OG exhibited an activity to induce apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. It induced BNIP3L level and facilitated physical associations of BNIP3L with Bcl-2 as well as Bcl-XL to set the mitochondrial Bax/Bak channels free for cytochrome c release. In addition, in vivo evaluation also showed that daily oral administration of OG was efficacious to prevent the tumor growth of PDAC cell grafts. Considering PDAC is a desmoplastic tumor consisting of many cancer-associated fibroblasts (CAFs), we further evaluated the efficacy of OG in a CAFs-involved PDAC mouse model. Endothelial-to-mesenchymal transition (EndoMT) is an important source of CAFs. The mix of EndoMT-derived CAFs with PDAC cell grafts significantly recruited myeloid-derived macrophages but prevented immune T cells. HSP90α secreted by EndoMT-derived CAFs further induced macrophage M2-polarization and more HSP90α secretion to expedite PDAC tumor growth. OG exhibited its potent efficacy against the tumor growth, M2-macrophages, and serum HSP90α level in the EndoMT-involved PDAC mouse model. CD91 and TLR4 are cell-surface receptors for extracellular HSP90α (eHSP90α). OG blocked eHSP90α-TLR4 ligation and, thus, prevented eHSP90α-induced M2-macrophages and more HSP90α secretion from macrophages and PDAC cells.

Increased in vitro leishmanicidal activity of octyl gallate loaded poly(methyl methacrylate) nanoparticles.

The current paucity of effective and affordable drugs for the treatment of leishmaniasis renders the search for new therapeutic alternatives a priority. Gallic acid-related compounds display anti-parasitic activities and their incorporation into drug carrier systems, such as polymeric nanoparticles may be a viable alternative for leishmaniasis treatment. Therefore, this study focused on the synthesis and characterization of octyl gallate (G8) loaded poly(methyl methacrylate) (PMMA) nanoparticles via miniemulsion polymerization in order to increase the leishmanicidal activity of this compound. G8 loaded PMMA nanoparticles presented a spherical morphology with a mean size of 108 nm, a negatively charged surface (-33 ± 5 mV) and high encapsulation efficiency (83% ± 5). Fourier-transform infrared spectroscopy and X-ray diffraction analysis confirmed that G8 was encapsulated in PMMA nanoparticles and presented a biphasic release profile. The G8 loaded PMMA nanoparticles did not present cytotoxic effect on human red blood cells. G8 loaded PMMA nanoparticles displayed a leishmanicidal activity almost three times higher than free G8 while the cytotoxic activity against human THP-1 cells remained unchanged.

Trapping of glyoxal by propyl, octyl and dodecyl gallates and their mono-glyoxal adducts.

Glyoxal (GO) is one of the major toxic intermediates generated during lipid oxidation and degradation. We investigated the inhibitory activities and mechanisms of propyl, octyl, and dodecyl gallates (PG, OG, and DG) on the formation of GO in buffer and during thermo-processing of corn oil, and the anti-carbonyl and antioxidative activities of the mono-GO adducts of PG, OG, and DG. Our results suggested that alkyl gallates could more effectively trap GO than gallic acid. The major mono-GO adducts of PG, OG, and DG were purified and their structures were elucidated based on their 1H, 13C, 2D-NMR, and HRMS data. We further demonstrated that the mono-GO (MG) adducts retained the anti-carbonyl and antioxidative activities. This is the first study to demonstrate that alkyl gallates, the popular food additives, could prevent not only food oxidation, but also the formation of toxic reactive carbonyl species and their corresponding advanced glycation end products (AGEs) during food processing.