Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis.

Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.

Ameliorating effects of selenium nanoparticle coated by gallic acid on histological and biochemical parameters of testis in azoospermic rat model.

This study was designed to examine the effects of selenium nanoparticles (SeNPs) coated with gallic acid (GA) on testis in azoospermic rats. Thirty-six adult Wistar rats were assigned to six groups: control (1 ml intraperitoneal (i.p.) phosphate-buffered saline (PBS) for 7 consecutive days), SHAM (single i.p. injection of 1 ml of 8 % dimethyl sulfoxide (DMSO)), BUS (single i.p. injection of busulfan (BUS) 30 mg/kg body weight), GA (single i.p. injection of BUS 30 mg/kg on day 1, 100 mg/kg body weight GA from days 2-7), SeNPs (single i.p. injection of BUS 30 mg/kg on day 1, 0.5 mg/kg body weight SeNPs from days 2-7), and SeNPs-GA (single i.p. injection of BUS 30 mg/kg on day 1, 0.5 mg/kg body weight SeNPs-GA from days 2-7). Subsequently, serum levels of testosterone and insulin-like growth factor-1 (IGF-1), antioxidant markers, sperm parameters, and histological parameters were evaluated. The results showed that BUS injection induced azoospermia in rats by causing oxidative stress and testicular tissue damage. In contrast, co-administration of SeNPs and GA showed significant improvements in testosterone and IGF-1 levels, antioxidant status, testicular tissue characteristics, and sperm parameters. Overall, the findings suggest that GA-coated SeNPs offer therapeutic potential in BUS-induced azoospermic models.

Chitosan grafted with gallic acid and cerium dioxide hybrid nanocomposites as environmentally friendly corrosion inhibitors for mild steel: An experimental and computational study.

Chitosan grafted with gallic acid (CS-GA), along with CS-GA doped with CeO2 nanoparticles (CS-GA-CeO2) were synthesized as novel environmentally friendly mild steel corrosion inhibitors. The formation of these derivatives was confirmed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), hydrogen nuclear magnetic resonance spectroscopy (1H NMR), and thermal analysis (TGA). Based on potentiodynamic polarization curves (PDP) measurements, the inhibitors acted primarily as hybrid inhibitors, while following the Langmuir adsorption theory model. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy(XPS) and 3D surface profiles, confirmed that CS-GA-CeO2 adsorbed on the mild steel forming a protective layer thus preventing the invasion of corrosive media. The corrosion protection mechanism of chitosan derivatives was investigated by molecular dynamics simulations. Electrochemical measurements were used to investigate the corrosion inhibition by CS-GA and CS-GA-CeO2 on mild steel in a 3.5 % NaCl solution. At room temperature, the highest inhibition efficiency (93.58 %) was achieved at 200 ppm CS-GA-CeO2. Modified chitosan nanocomposites were confirmed as promising corrosion inhibitors.

Novel eco-friendly and easily recoverable bismuth-based materials for capturing and removing polyphenols from water.

Olive oil production is one of the most developed Europe's sectors, producing olive oil and undesirable by-products, such as olive mill wastewater (OMWW) and organic waste. OMWW, containing large amounts of compounds (mainly polyphenols, phenols, and tannins), represents a problem. In fact, polyphenols have dual nature: i) antioxidant beneficial properties, useful in many industrial fields, ii) biorefractory character making them harmful in high concentrations. If not properly treated, polyphenols can harm biodiversity, disrupt ecological balance, and degrade water quality, posing risks to both environment and human health. From a circular economy viewpoint, capturing large quantities of polyphenols to reuse and removing their residuals from water is an open challenge. This study proposes, for the first time, a new path beyond the state-of-the-art, combining adsorption and degradation technologies by novel, eco-friendly and easily recoverable bismuth-based materials to capture large amounts of two model polyphenols (gallic acid and 3,4,5-trimethoxybenzoic acid), which are difficult to remove by traditional processes, and photodegrade them under solar light. The coupled process gave rise to collect 98% polyphenols, and to rapidly and effectively photodegrade the remaining portion from water.

Cytoprotective Effect of Gallic Acid against Injuries Promoted by Therapeutic Ionizing Radiation in Preosteoblast Cells.

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs.

Exploring the synergistic potential of pomegranate fermented juice compounds against oxidative stress-induced neurotoxicity through computational docking and experimental analysis in human neuroblastoma cells.

This study explored the neuroprotective potential of fermented pomegranate (PG-F) against hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanisms. The fermentation process, involving probiotics, transforms the hydrolyzable tannins in pomegranate juice into ellagic acid (EA) and gallic acid (GA), which are believed to contribute to its health benefits. Molecular docking simulations confirmed the stable interactions between EA, GA, and proteins associated with the antioxidant and anti-apoptotic pathways. PG-F significantly enhanced the viability of H2O2-treated cells, as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, cell morphology observations, and Hoechst 33342 staining. PG-F mitigated the H2O2-induced intracellular reactive oxygen species (ROS) levels, restored mitochondrial membrane potential, and upregulated antioxidant gene expression. The PG-F treatment also attenuated the H2O2-induced imbalance in the Bax/Bcl-2 ratio and reduced the cleaved caspase-3, caspase-7, and caspase-9 levels, suppressing the apoptotic pathways. Further insights showed that PG-F inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and facilitated the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2), highlighting its role in modulating the key signaling pathways. A combined treatment with equivalent concentrations of EA and GA, as found in PG-F, induced remarkable cellular protection. Drug combination analysis using the Chou-Talalay method revealed a synergistic effect between EA and GA, emphasizing their combined efficacy. In conclusion, PG-F has significant neuroprotective effects against H2O2-induced neurotoxicity by modulating the antioxidant and anti-apoptotic pathways. The synergistic action of EA and GA suggests the therapeutic potential of PG-F in alleviating oxidative stress-associated neurodegenerative diseases.

Improving the physicochemical quality and oxidative stability of deep-fried pork meatballs by coating with chitosan grafted gallic acid.

The objective of this research was to examine the effectiveness of chitosan (CH)-gallic acid (GA) conjugate (CH-g-GA) as an edible coating in improving the physicochemical properties and oxidative stability of deep-fat fried pork meatballs. The meatballs were coated with either CH alone, a combination of CH and GA, or CH-g-GA before being fried at 180 °C for 5 min. The viscosity of the coating solutions influenced the amount of coating picked up by the meatballs, with higher viscosity coatings showing increased pickup. The application of chitosan-based coatings in deep-fried meatballs resulted in a decrease in moisture loss and oil uptake, as well as decreased b* values and hardness, while maintaining consistent cooking yield. Furthermore, compared to the control group, the chitosan-based coatings treatment significantly increased the ratio of immobilized water and decreased the ratio of free water (P < 0.05), as well as effectively inhibited lipid oxidation in deep-fried meatballs (P < 0.05). Among the different coatings tested, CH-g-GA coating exhibited the highest effectiveness. The research findings suggest that the CH-g-GA edible coating has significant potential in enhancing the overall quality of deep-fried meatballs.

Synthesis, in vitro and in silico evaluation of gallamide and selenogallamide derivatives as inhibitors of the SARS-CoV-2 main protease.

The present work reports the inhibitory effect of amides derived from gallic acid (gallamides) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), along with cytotoxicity evaluation and molecular docking studies. In addition to gallamides, other relevant compounds were also synthesized and evaluated against Mpro, making a total of 25 compounds. Eight compounds presented solubility issues during the inhibitory assay and one showed no inhibitory activity. Compounds 3a, 3b, and 3f showed the highest enzymatic inhibition with IC50 = 0.26 ± 0.19 µM, 0.80 ± 0.38 µM, and 2.87 ± 1.17 µM, respectively. Selenogallamide 6a exhibited IC50 values of 5.42 ± 2.89 µM and a comparison with its nonselenylated congener 3c shows that the insertion of the chalcogen moiety improved the inhibitory capacity of the compound by approximately 10 times. Regarding the cellular toxicity in THP-1 and Vero cells, compounds 3e and 3g, showed moderate cytotoxicity in Vero cells, while for THP-1 both were nontoxic, with CC50 > 150 µM. Derivative 3d showed moderate cytotoxicity against both cell lines, whereas 6d was moderatly toxic to THP-1. Other compounds analyzed do not induce substantial cellular toxicity at the concentrations tested. The molecular docking results for compounds 3a, 3b, and 3f show that hydrogen bonding interactions involving the hydroxyl groups (OH) of the gallate moiety are relevant, as well as the carbonyl group.

Gallic acid loaded self-nano emulsifying hydrogel-based drug delivery system against onychomycosis.

Aim: To developed and investigate gallic acid (GA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) for treating onychomycosis via transungual route. Materials & methods: The SNEDDS were prepared by direct dispersion technique and were evaluated for characteristics parameters using Fourier transform infrared, differential scanning calorimetry, confocal microscopy, transmission electron microscopy and zeta sizer. Furthermore, the safety of prepared formulation was evaluated via Hen's egg test-chorioallantoic membrane study and stability was confirmed using different parameters. Also, its effectiveness was evaluated against fungal strain Trichophyton mentagrophytes. Results: The SNEDDS displayed a particle size of 199.8 ± 4.21 nm and a zeta potential; of -22.75 ± 2.09 mV. Drug release study illustrated a sustained release pattern with a release of 70.34 ± 0.20% over a period of 24 h. The penetration across the nail plate was found to be 1.59 ± 0.002 µg/mg and 0.97 ± 0.001 µg/mg for GA loaded SNEDDS and GA solution respectively. An irritation score of 0.52 ± 0.005 and 3.84 ± 0.001 was reported for GA loaded SNEDDS hydrogel and GA solution, indicating a decrease in the drug's irritation potential from slightly irritating to non irritating due to its entrapment within the SNEDDS. Conclusion: GA loaded SNEDDS has potential to address limitations of conventional treatments, enhancing the drug's efficacy and reducing the likelihood of resistance in the treatment of Onychomycosis.

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Biosensor-based active ingredient recognition system for screening potential small molecular Severe acute respiratory syndrome coronavirus 2 entry blockers targeting the spike protein from Rugosa rose.

The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 µM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 µM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.

Metabolic and gene-expression analyses reveal developmental dynamics of cutin deposition in pomegranate fruit grown under different environmental conditions.

The chemical and transcriptional changes in the cuticle of pomegranate (Punica granatum L.) fruit grown under different environmental conditions were studied. We collected fruit from three orchards located in different regions in Israel, each with a distinct microclimate. Fruit were collected at six phenological stages, and cutin monomers in the fruit cuticle were profiled by gas chromatography-mass spectrometry (GC-MS), along with qPCR transcript-expression analyses of selected cutin-related genes. While fruit phenotypes were comparable along development in all three orchards, principal component analyses of cutin monomer profiles suggested clear separation between cuticle samples of young green fruit to those of maturing fruit. Moreover, total cutin contents in green fruit were lower in the orchard characterized by a hot and dry climate compared to orchards with moderate temperatures. The variances detected in total cutin contents between orchards corresponded well with the expression patterns of BODYGUARD, a key biosynthetic gene operating in the cutin biosynthetic pathway. Based on our extraction protocols, we found that the cutin polyester that builds the pomegranate fruit cuticle accumulates some levels of gallic acid-the precursor of punicalagin, a well-known potent antioxidant metabolite in pomegranate fruit. The gallic acid was also one of the predominant metabolites contributing to the variability between developmental stages and orchards, and its accumulation levels were opposite to the expression patterns of the UGT73AL1 gene which glycosylates gallic acid to synthesize punicalagin. To the best of our knowledge, this is the first detailed composition of the cutin polyester that forms the pomegranate fruit cuticle.

The variation of acrylamide and 5-hydroxymethylfurfural in tea with different roasting degrees and the effects of tea polyphenols on their formation.

BACKGROUND: Roasting is an essential step in making roasted teas, and its role in producing flavors has been widely studied. However, the variation of potential hazardous compounds during the tea roasting process is still vague. The present study established an effective method based on liquid chromatography-triple quadrupole-tandem mass spectrometry to simultaneously determine the variation of acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and free amino acids during the tea roasting process. Meanwhile, the effects of several tea polyphenols on the formation of AA and 5-HMF were investigated by a wet-to-dry thermal model reaction. RESULTS: Medium-temperature roasted teas had the highest levels of AA and 5-HMF, with ranges of 0.13-0.15 µg g-1 and 68.72-123.98 µg g-1, respectively. Quantitative results showed that the levels of monosaccharides and amino acids decreased during roasting, which might contribute to the formation of 5-HMF and AA. Meanwhile, the decrease of epigallocatechin gallate (EGCG), epigallocatechin (EGC), and epicatechin (EC) might be related to their inhibitory effects on 5-HMF and AA. Thermal model reaction results showed that EGCG and EC significantly inhibited 5-HMF formation with a decline rate of 33.33% and 72.22%, respectively, mainly by trapping glucose. Gallic acid (GA) also had an inhibitory effect on the formation of AA (decreased by 92.86%) and 5-HMF (44.44%), mainly through impeding the preliminary reaction of asparagine and glucose. CONCLUSION: The roasting temperature determined the levels of AA and 5-HMF in teas. Catechins inhibited the formation of 5-HMF and AA mostly through trapping monosaccharides, while the inhibitory effect of GA was achieved by impeding the reaction. © 2024 Society of Chemical Industry.

Metabolic basis for superior antioxidant capacity of red-fleshed peaches.

Peach fruit is an important natural source of phenolic compounds that are well-known to have health benefits, but their metabolic basis remain elusive. Here, we report on phenolic compounds accumulation and antioxidant activity of ripe fruits in peach. A considerable variation in phenolic compounds content was observed among peach germplasm, with significantly higher levels detected in red-fleshed peaches compared to non-red-fleshed peaches. Antioxidant activity of crude extracts from ripe fruits showed significant differences among peach germplasm, with red-fleshed peaches having the strongest antioxidant activity. Intriguingly, it was observed that total phenolics instead of anthocyanins were strongly associated with antioxidant activity. Phenolic compounds content and antioxidant activity showed dynamic changes throughout fruit development, and these were much higher in the peel than in the flesh. Metabolomic analysis unveiled a coordinated accumulation of anthocyanins as well as key components of flavonoids and phenolic acids, which endows red-fleshed peaches with superior antioxidant activity.

Graphitic carbon @ silver nanoparticle @ porous silicon Bragg mirror composite SERS substrate for gallic acid detection.

Graphite carbon (G) @ silver (Ag) @ porous silicon Bragg mirror (PSB) composite SERS substrate was successfully synthesized using electrochemical etching (ec) and hydrothermal carbonization (HTC) techniques with silver nitrate as the source of silver and glucose as the source of carbon. The PSB was used as a functional scaffold for the synthesis of graphite-carbon and silver composite nanoparticles (G@AgNPs) on its surface, thereby combining SERS activity and antioxidant properties. To our knowledge, this is the first time that G@AgNPs has been synthesized on the PSB using glucose as a carbon source. The synthesized G@Ag@PSB was utilized as a SERS platform for the detection of gallic acid (GA). Test results demonstrated that the substrate exhibited a remarkable SERS enhancement capability for GA, with the enhancement factor (EF) reaching 2 × 105. The reproducibility of the SERS spectral signal was excellent, with a relative standard deviation (RSD) of 7.5 %. The sensitivity test results showed that the linear range of GA detection based on G@Ag@PSB composite SERS substrate was 2 × 10-3-2 × 10-12M. The relationship between GA concentration and SERS signal intensity exhibited a strong linear correlation, with a linear correlation coefficient (R2) of 0.97634. Moreover, even with an extended storage period, only a marginal decline in the signal intensity of GA on the substrate was observed. The results of this study demonstrate that the prepared G@Ag@PSB composite SERS substrate had good potential application performance as a low-cost SERS detection platform suitable for commercial use. In addition, this advance facilitates the further exploration of more nanomaterials with ultra-high sensitivity in SERS technology.

Ameliorative effects of gallic acid on tebuconazole-induced adverse effects in the cerebellum of adult albino rats: histopathological and immunohistochemical evidence.

Tebuconazole (TEB) is a common triazole sterol demethylation inhibitor fungicide utilized to manage a variety of diseases in crops like cereals, fruits, and vegetables. The aim of this work was to assess the effects of TEB on the structure of the cerebellum in adult albino rats and possible protective impact of co-administration of Gallic acid (GA). Four groups of forty adult male albino rats were randomly selected, and the rats in group I received corn oil through daily gavage for 4 weeks. Group II received GA dissolved in the normal saline at a dose of 100 mg/kg through daily gavage for 4 weeks, group III administered with TEB dissolved in corn oil at its acceptable daily intake dose (0.02 mg/kg body weight) through daily gavage for 4 weeks, group IV rats received both TEB and GA. For light microscopic, ultrastructural, and immunohistochemical investigations, cerebellar specimens were prepared. TEB exposure led to neuronal damage in the form of degenerated Purkinje cells with vacuolated cytoplasm, areas of lost Purkinje cells, the basket cells appeared vacuolated with degenerated neuropil, the granule cells clumped with congested areas between them, dilated cerebellar islands, weak positive bcl2 immunoreactions in the Purkinje cells, and numerous GFAP-positive astrocytes. GA mitigated TEB-mediated histological changes in the cerebellar cortex. We concluded that TEB caused Purkinje neurons in the rat cerebellar cortex to degenerate and undergo apoptosis. GA had a neuroprotective benefit against TEB toxicity in the rat cerebellar cortex.

Controlled release characteristics of alkyl gallates and gallic acid from ß-cyclodextrin inclusion complexes of alkyl gallates.

The freeze-drying approach was used to create inclusion complexes utilizing alkyl gallates and ß-cyclodextrin, namely dodecyl gallate, octyl gallate, butyl gallate, and ethyl gallate, which are exemplary examples of phenolic esters. The everted-rat-gut-sac model demonstrated that the inclusion complexes released alkyl gallates, which were subsequently hydrolyzed to generate free gallic acid, as evidenced by HPLC-UV analysis. Both gallic acid and short-chain alkyl gallates were capable of permeating the small intestinal membrane. The transport rate of gallic acid (or alkyl gallates) exhibited an initial rise followed by a drop when the carbon-chain lengths varied. The inclusion complex groups exhibited a superior sustained-release effect compared to the comparable alkyl gallates groups, thus possibly leading to higher bioavailability and stronger bioactivity. Moreover, altering the length of the carbon chain will allow for the effortless achievement of regulated release of phenolic compounds and short-chain phenolic esters from such ß-cyclodextrin inclusion complexes.

Flexible and wearable sensor for in situ monitoring of gallic acid in plant leaves.

Gallic acid (GA) is one of the main phenolic components naturally occurring in many plants and foods and has been a subject of increasing interest owing to its antioxidant and anti-mutagenic properties. This study introduces a novel flexible sensor designed for in situ detecting GA in plant leaves. The sensor employs a laser-induced graphene (LIG) flexible electrode, enhanced with MXene and molybdenum disulfide (MoS2) nanosheets. The MXene/MoS2/LIG flexible sensor not only demonstrates exceptional mechanical properties, covering a wide detection range of 1-1000 µM for GA, but also exhibits remarkable selectivity and stability. The as-prepared sensor was successfully applied to in situ determination of GA content in strawberry leaves under salt stress. This innovative sensor opens an attractive avenue for in situ measurement of metabolites in plant bodies with flexible electronics.

In Vitro Antiviral Activity of Rhodiola crenulata Extract against Zika Virus and Japanese Encephalitis Virus: Viral Binding and Stability.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) can cause permanent neurological damage and death, yet no approved drugs exist for these infections. Rhodiola crenulate, an herb used in traditional Chinese medicine for its antioxidation and antifatigue properties, was studied for its antiviral activity against ZIKV and JEV in vitro. The cytotoxicity of Rhodiola crenulata extract (RCE) was evaluated using the CCK-8 reagent. Antiviral effects of RCE were assessed in ZIKV-infected or JEV-infected Vero cells via quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, fluorescent focus assay (FFA), and immunofluorescence assay (IFA). The cell-free antiviral effects of RCE were evaluated using an inactivation assay. To determine the stage of the viral life cycle affected by RCE, time-of-addition, binding, and entry assays were conducted. Three bioactive constituents of RCE (salidroside, tyrosol, and gallic acid) were tested for antiviral activity. RCE exhibited dose-dependent anti-ZIKV and anti-JEV activities at non-cytotoxic concentrations, which were likely achieved by disrupting viral binding and stability. Gallic acid exhibited antiviral activity against ZIKV and JEV. Our findings indicate that RCE disrupts viral binding and stability, presenting a potential strategy to treat ZIKV and JEV infections.

A Mitochondria-Targeted Heptamethine Indocyanine Small Molecular Chelator for Attenuating Uranium Nephrotoxicity.

Radionuclide uranium has both a chemical and radioactive toxicity, leading to severe nephrotoxicity as it predominantly deposits itself in the kidneys after entering into human bodies. It crosses renal cell membranes, accumulates in mitochondria and causes mitochondrial oxidative damage and dysfunction. In this study, a mitochondria-targeted heptamethine indocyanine small molecule chelator modified with gallic acid (IR-82) is synthesized for uranium detoxication. Both gallic acid and sulfonic acid, as two hydrophilic endings, make IR-82, being excreted feasibly through kidneys. Gallic acid with polyphenol groups has a steady metal chelation effect and potent antioxidant ability, which may facilitate IR-82-alleviated uranium nephrotoxicity simultaneously by enhancing uranium decorporation from the kidneys and reducing mitochondrial oxidative damage. Cell viability assays demonstrate that IR-82 can significantly improve the cell viability of uranium-exposed human renal (HK-2) cells. It is also demonstrated to accumulate in mitochondria and reduce mitochondrial ROS and total intracellular ROS, as well as intracellular uranium content. In vivo imaging experiments in mice show that IR-82 could be excreted out through kidneys. ICP-MS tests further reveal that IR-82 can efficiently decrease the uranium deposition in mouse kidneys. IR-82 treatment improves the animal survival rate and renal function of experimental mice after high-dose uranium exposure. Collectively, our study may evidence that the development of uranium decorporation agents with kidney-mitochondrion dual targeting abilities is a promising strategy for attenuating uranium-induced nephrotoxicity.

Clicking gallic acid into chitosan prolongs its antioxidant activity and produces intracellular Ca2+ responses in rat brain cells.

Gallic acid is a vegetable-derived and highly bioactive phenolic acid, but its antioxidant capacity is sensitive to environmental conditions. Chitosan is a biopolymer capable of exerting significant protection to various molecules, including phenolic compounds. A chitosan derivative that extends the antioxidant activity of gallic acid was synthesized by click chemistry and characterized by FT-IR, 1H NMR, and antioxidant capacity assays. Our results show that synthesized polymeric solutions and nanoparticles of N-(gallic acid) chitosan were both internalized by rat brain cells, processes that were modulated by extracellular Ca2+ and Na+. Their internalization was supported by dynamic light scattering and ζ-potential analyses, while Ca2+ imaging recordings performed in brain cells revealed the potential biological effect of N-(gallic acid) chitosan. We conclude that the synthesis of an N-(gallic acid) chitosan derivative through click chemistry is viable and may serve as strategy to prolong its antioxidant activity and to study its biological effects in vivo.