Elimination Of Free Radicals Research Articles

Pretreatment with aqueous Moringa oleifera Lam. leaf extract prevents cadmium-induced hepatotoxicity by improving cellular antioxidant machinery and reducing cadmium accumulation

Cadmium (Cd) is a highly harmful pollutant that poses a serious threat to human health. The liver is the primary organ for Cd accumulation, and Cd-induced hepatotoxicity has been shown to be strongly correlated with an oxidative imbalance in hepatocytes. Our previous studies in the eukaryotic model organism Saccharomyces cerevisiae revealed that not only co-treatment but also pretreatment with aqueous Moringa oleifera Lam. leaf extract (AMOLE) effectively mitigated Cd toxicity by reducing intracellular Cd accumulation and Cd-mediated oxidative stress. In this study, we therefore investigated the preventive effect of AMOLE against Cd toxicity in human HepG2 hepatocytes. The results showed that, similar to the case of the yeast model, pretreatment with AMOLE prior to Cd exposure also significantly inhibited Cd-induced oxidative stress in HepG2 cells. Untargeted LC-MS/MS-based metabolomic analysis of AMOLE revealed that its major phytochemical constituents were organic acids, particularly phenolic acids and carboxylic acids. Additionally, DPPH-HPTLC fingerprints suggested that quercetin and other flavonoids possibly contribute to the antioxidant activities of AMOLE. Based on our findings, it appears that pretreatment with AMOLE prevented Cd-induced hepatotoxicity via three possible mechanisms: i) direct elimination of free radicals by AMOLE antioxidant compounds; ii) upregulation of antioxidant defensive machinery (GPx1, and HO-1) via Nrf2 signaling cascade to improve cellular antioxidant capacity; and iii) reduction of intracellular Cd accumulation, probably by suppressing Cd uptake. These data strongly suggest the high potential of AMOLE for clinical utility in the prevention of Cd toxicity.

Inhibitory effects of cold plasma-activated water on the generation of advanced glycation end products and methylimidazoles in cookies and mechanistic evaluation using electron paramagnetic resonance

The inhibitory effects of cold plasma-activated water (PAW) on the formation of AGEs and methylimidazoles in cookies was examined. The results showed that different PAW (parameters: 50 W–50 s, 50 W–100 s, 50 W–150 s, 100 W–50 s, 100 W–100 s, and 100 W–150 s) reduced the contents of AGEs and methylimidazoles, in which the maximum inhibition rates were 47.38% and 40.17% for free and bound AGEs and 44.16% and 40.31% for free and bound methylimidazoles, respectively. Moreover, the mechanisms associated with the elimination of carbonyl intermediates and free radicals was determined by electron paramagnetic resonance (EPR) and high performance liquid chromatography-ultraviolet/visible absorption detector (HPLC-UV/Vis). The results showed the quenching of total free radicals, alkyl free radicals, and HO· by PAW, leading to the suppression of glyoxal and methylglyoxal intermediates. These findings support PAW as a promising agent to enhance the safety of cookies.

Double quenching electrochemiluminescence aptsensor based on free radical elimination and resonance energy transfer for the sensitive detection of zearalenonea

Zearalenone (ZEN) has serious impacts on human and animal health due to its mutagenicity, teratogenicity, carcinogenicity, immunotoxicity, and genetic toxicity. In this study, an electrochemiluminescence (ECL) aptsensor for ultrasensitive ZEN detection was constructed based on the double quenching effect of CM-MOFs. Luminol was fixed on the gold nanoparticle-modified Prussian blue analogs (Au NPs@PBAs) with catalytic activity by Au-NH2 to obtain Lu@Au@PBAs with stable and strong signal output. Bimetallic porphyrin metal-organic frameworks (CM-MOFs) improve the sensitivity of aptsensors through radical elimination and resonance energy transfer strategies. The experimental data shows that the dynamic detection range of the aptsensor is 500 fg/mL∼100 ng/mL, and the limit of detection is as low as 0.37 pg/mL. The aptsensor is proven to be suitable for the detection of ZEN in corn flour and has strong practicability. It is important that the ECL detection strategy can be used to detect other similar analytes and has a wide range of potential applications in food analytical detection.

Association of mRNA expression and polymorphism of antioxidant glutathione-S-transferase (GSTM1 and GSTT1) genes with the risk of Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus (GDM) is a medical complication during the gestational period in which woman who had never been diagnosed with diabetes develops hyperglycemia. Prior studies have demonstrated that the advancement of GDM and its consequences arises from a disparity between oxidants and antioxidants in the cells. The observed outcomes can be attributed to an excessive formation of reactive oxygen species (ROS) within the cells, coupled with a reduced activity of anti-oxidative enzymes. Glutathione S-transferase (GSTs) is recognized as an antioxidant enzyme that is belong to as a phase II family member of detoxifying enzymes. These metabolic multigene catalysts are found into the cytoplasm of the cell. GSTs play a vital part in the elimination of cellular ROS or free radicals. The study involves total 300 pregnant women, (150 GDM cases and 150 healthy controls). The polymorphism study of GSTs genes (GSTM1 and GSTT1) was determined by conventional Polymerase Chain Reaction (PCR). The mRNA expression study of GSTM1 and GSTT1 genes analysed by qPCR/ RT-PCR (quantitative PCR/Real-Time PCR) followed by statistical analysis done using Prism8 software (version 8.01). The study revealed statistically significant variations in biochemical parameters between GDM cases and controls. It was found GSTM1-null (GSTM1-/-) polymorphism significantly (P < 0.0001) most prevalent in GDM cases (56.7%) when compared to healthy control (28%). However, no significant difference was observed for GSTT1 null and present polymorphism (P = 0.906). The gene expression levels of both GSTM1 and GSTT1 were found considerably downregulated in individuals with GDM as compared to the control group (P < 0.0001). The downregulation of gene expression has a significant (P<0.0001) association with the null/deletion polymorphism of both GSTM1/ GSTT1 genes respectively. Null/deletion genotype of GSTM1 gene and its expression showed significant association with GDM. Therefore, this gene variant has the potential to be used as a prognostic biomarker for GDM. However, there is need to study this gene variant in larger sample size and different ethnicity.

D-Tagatose: A Rare Sugar with Functional Properties and Antimicrobial Potential against Oral Species.

Carbohydrates have a dietary role, but excessive consumption of high-calorie sugars can contribute to an increased incidence of metabolic diseases and dental caries. Recently, carbohydrates with sweetening properties and low caloric value, such as D-tagatose, have been investigated as alternative sugars. D-tagatose is a rare sugar that has nutritional and functional properties of great interest for health. This literature review presents an approach to the biological effects of D-tagatose, emphasizing its benefits for oral health. Studies report that D-tagatose has antioxidant and prebiotic effects, low digestibility, reduced glycemic and insulinemic responses, and the potential to improve the lipid profile, constituting an alternative for diabetes mellitus and obesity. It can also be observed that D-tagatose has an antioxidant action, favoring the elimination of free radicals and, consequently, causing a reduction in cellular oxidative stress. Furthermore, it also has antibacterial potential against oral species. Regarding oral health, studies have shown that D-tagatose efficiently reversed bacterial coaggregations, including periodontopathogenic species, and impaired the activity and growth of cariogenic bacteria, such as S. mutans. D-tagatose significantly inhibited biofilm formation, pH decrease and insoluble glucan synthesis in S. mutans cultures. Salivary S. mutans counts were also significantly reduced by the consumption of chewing gum containing D-tagatose and xylitol. In addition, there is evidence that tagatose is effective as an air-polishing powder for biofilm decontamination. The literature indicates that D-tagatose can contribute to the prevention of systemic diseases, also constituting a promising agent to improve oral health.

Anti-inflammatory peptide therapeutics and the role of sulphur containing amino acids (cysteine and methionine) in inflammation suppression: A review.

Inflammation serves as our body's immune response to combat infections, pathogens, viruses, and external stimuli. Inflammation can be classified into two types: acute inflammation and chronic inflammation. Non-steroidal anti-inflammatory medications (NSAIDs) are used to treat both acute and chronic inflammatory disorders. However, these treatments have various side effects such as reduced healing efficiency, peptic ulcers, gastrointestinal toxicities, etc. METHOD: This review assesses the potential of anti-inflammatory peptides (AIPs) derived from various natural sources, such as algae, fungi, plants, animals, and marine organisms. Focusing on peptides rich in cysteines and methionine, sulphur-containing amino acids known for their role in suppression of inflammation. Due to their varied biological activity, ability to penetrate cells, and low cytotoxicity, bioactive peptides have garnered interest as possible therapeutic agents. The utilisation of AIPs has shown great potential in the treatment of disorders associated with inflammation. AIPs can be obtained from diverse natural sources such as algae, fungi, plants, and animals. Cysteine and methionine are sulphur-containing amino acids that aid in the elimination of free radicals, hence assisting in the treatment of inflammatory diseases. This review specifically examines several sources of AIPs including peptides that contain numerous cysteines and methionine. In addition, the biological characteristics of these amino acids and advancements in peptide delivery are also discussed.

Highly Biocompatible Composites as Cigarette Smoke Purifiers for Free Radical Scavenging and Pungent Odor Masking

AbstractThe modification of cigarette filters with nanozymes has gradually emerged as a promising strategy for reducing the harmful effects of smoking by eliminating excessive harmful free radicals and remediating oxidative stress‐induced pulmonary injury. However, currently, available nanozymes‐integrated filters usually ignore safety concerns and fail to address the pungent odor of smoke, making it challenging to develop an individual system with high safety and effectiveness while considering these important factors. Herein, a novel smoke purifier (CDs/ME@MOF) is developed by alternatively introducing carbon dots nanozymes with excellent free radicals scavenging activity and Menthone masking the miscellaneous gas into a biocompatible γ‐cyclodextrin‐based metal–organic framework. The CDs/ME@MOF can act as a profitable additive incorporated with cigarette filters to achieve over 90% scavenging efficiency for cigarette smoke radicals and reduce the odor irritation. In the mice model, the CDs/ME@MOF composites demonstrated the significant inflammation suppression, antioxidant levels promotion, and notable lung tissues protection effect through elimination of free radicals. This work highlights the potential of CDs/ME@MOF as a safe, environmentally friendly, and multipurpose additive for modifying cigarette filter.

GCMS-based Phytochemical Profiling of L. camara Induces Apoptosis and Cell Cycle Arrest in Lung Cancer

In this paper, the focus is on the phytochemical study of Lantana camara L. leaf extract, specifically its antioxidant and anti-cancer effects. The study shows that all solvent extracts have significant antioxidant and anticancer activity. However, the methanol liquid extract of L. camara leaf contains higher levels of metabolites than other solvents. The methanolic extracts of the leaves of four distinct species of Lantana camara also have high levels of terpenoid chemicals, which demonstrate strong antioxidant and free radical elimination properties. With further research, it is possible that useful medications can be developed for the treatment of various human diseases, especially lung cancer.

Efficient Catalytic Degradation of Methyl Orange by Various ZnO-Doped Lignin-Based Carbons.

Herein, a series of ZnO-doped lignin-based carbons (LC/ZnO) were successfully prepared from different types of lignin and used for methyl orange (MO) photocatalytic degradation. The apparent morphology, internal structure, and photoelectric properties of prepared LC/ZnO composites and their effects on subsequent MO photocatalytic degradation were investigated by various characterization techniques. The results showed that the LC/ZnO composites that were prepared in this work mainly consisted of highly dispersed ZnO nanoparticles and lignin-based carbon nano-sheets, which were beneficial for subsequent photogenerated electrons and holes formation, dispersion, and migration. The MO could be significantly degraded with various ZnO-doped lignin-based carbons, especially over the LCSL/ZnO, and the maximum degradation rate was 96.9% within 30 min under the simulated 300w sunlight exposure. The experiments of free radical elimination showed that the photocatalytic degradation of MO over LC/ZnO were a result of the co-action of multiple free radicals, and h+ might play the predominant roles in MO degradation. In addition, the pH of the solution had little effect on MO degradation, and the MO could be effectively degraded even in an alkaline solution of pH = 12.0. The cycling experiments showed that the prepared LC/ZnO had a good stability for MO photodegradation, especially for LCSL/ZnO, even after 5 times recycling, and the degradation rate of MO only dropped from 97.0% to 93.0%. The research not only provided a fundamental theory for the efficient photocatalytic degradation of MO by LC/ZnO composites, but also offered a new insight into lignin valorization.

Dual-Responsive Nanogels with Cascaded Gentamicin Release and Lysosomal Escape to Combat Intracellular Small Colony Variants for Peritonitis and Sepsis Therapies.

Intracellular bacteria are the major cause of serious infections including sepsis and peritonitis, but face great challenges in fighting against the stubborn intracellular small colony variants (SCVs). Herein, the authors have developed nanogels (NGs) to destroy both planktonic bacteria and SCVs and eliminate excessive inflammations for peritonitis and sepsis therapies. Free gentamicin (GEN) and hydroxyapatite nanoparticles (NPs) with GEN loading and mannose grafts (mHAG) are inoculated into ε-polylysine NGs to obtain NG@G1-mHAG2 through crosslinking with phenylboronic acid and tannic acid. The H2O2 consumption after reaction with phenylboronic esters and the elimination of free radicals by tannic acid alleviates the escalated inflammatory status to promote sepsis therapy. After mannose-mediated uptake into macrophages, the acid-triggered degradation of mHAG NPs generates Ca2+ to destabilize lysosomes and the efficient lysosomal escape leads to reversion of hypometabolic SCVs into normal phenotype and their sensitivity to GEN. In a peritonitis mouse model, NG@G1-mHAG2 treatment provides strong and persistent bactericidal effects against both extracellular bacteria and intracellular SCVs and extends survival of peritonitis mice without apparent hepatomegaly, splenomegaly, pulmonary edema, and inflammatory cell infiltration. Thus, this study demonstrates a concise and versatile strategy to eliminate SCVs and relieve inflammatory storms for peritonitis and sepsis therapies without infection recurrence.

Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.

β(1,3) β(1,6) glucogalactan from Rhizopus microsporus var. oligosporus: extraction, characterization, antioxidant and α-amylase inhibitory activities.

In this study, the Box-Behnken experimental planning was used to optimize the extraction of polysaccharides from the cell wall of Rhizopus microspore var. oligosporus, with analysis of the quantitative effects of parameters pH, temperature and extraction time for polysaccharide yield. The optimal conditions for extraction were determined by the regression equation and evaluation of the response surface graphs, which indicated: pH 13, temperature of 120ºC and time of 60 min, with maximum yield around 18.5%. Fourier transform infrared spectroscopy analysis indicated typical polysaccharide signals. Nuclear magnetic resonance spectroscopy and monosaccharide analysis indicated a β(1,3) β(1,6) glucogalactan. The polysaccharide exhibited an average molecular weight of 120 kDa and a polymerization degree of 741. Antioxidant assays in vitro revealed the potential of polysaccharide in elimination of ABTS+ radical and hydroxyl radicals. EC50 values for free radical elimination were 7.69 and 17.8 mg/mL, for ABTS+ and hydroxyls, respectively. The polysaccharides showed potential for α-amylase inhibition with an EC50 of 1.66 mg/mL. The results suggest that β(1,3) β(1,6) glucogalactan from Rhizopus microsporus var. oligosporus can be used in biotechnological applications.

Conformationally regulated “nanozyme-like” cerium oxide with multiple free radical scavenging activities for osteoimmunology modulation and vascularized osseointegration

Given post-operative aseptic loosening in orthopedic disease treatment, osteointegration occurs at the bone-implant interface as a holistic process, including immunoregulation (e.g., macrophage polarization), angiogenesis and osteogenesis in sequence. In order to achieve early rapid and satisfactory osseointegration, different nano-shaped (nanocone, nanopolyhedron and nanoflower abbr. NC, NP & NF) cerium oxide (CeO2-x) coatings, endowed with “nanozyme-like” activities for multiple free radical elimination and osteoimmunology regulation, were hydrothermally synthesized on titanium alloy (TC4). In vitro cell experiments showed that nano-CeO2-x coated TC4 not only induced polarization of RAW264.7 cells toward M2 phenotype, but also promoted angiogenesis and vascularization of endothelial cells along with differentiation and mineralization of osteogenic precursor cells. Improvements in M2-polarized macrophage, angiogenesis, and bone regeneration were further confirmed in a rat femoral condyle model. Among the above three nano-morphologies, NF exhibited the best osseoinetegration. RNA sequencing and mechanism exploration suggested that the inhibition of PI3K-AKT signaling pathway was essential for immunomodulatory capacity of NF. In conclusion, it provided promising insights into the immunomodulatory exploitation of orthopedic implants.

Grape seed proanthocyanidins regulate mitophagy of endothelial cells and promote wound healing in mice through p-JNK/FOXO3a/ROS signal pathway

Skin wound healing is a dynamic and complex process that involves multiple physiological and cellular events. Grape seed proanthocyanidins (GSP) have strong anti-oxidation and elimination of oxygen free radicals, and have been shown to significantly promote wound healing, but the underlying mechanism remains unclear. Studies have indicated that reactive oxygen species (ROS) acts as an upstream signal to induce mitophagy, suggesting that GSP can regulate mitophagy through the signal pathway. This study aimed to investigate whether GSP regulates mitophagy by down-regulating oxidative stress to promote wound healing. In vivo, GSP treatment accelerated wound healing, granulation tissue formation, collagen deposition, and angiogenesis in mice. Moreover, GSP down-regulated ROS levels and promoted the expression of antioxidant proteins by up-regulating the expression of p-JNK/FOXO3a protein, thereby regulating the expression of mitophagy-related proteins. In vitro, 4 μg/mL GSP showed no apparent toxic effects on cells and effectively reduce the oxidative stress damage of cells induced by H2O2. Western blot and superoxide anion fluorescence probe further confirmed that GSP effectively reduced Dihydroethidium content and up-regulated the expression of antioxidant proteins by activation of p-JNK/FOXO3a protein expression, thereby regulating mitophagy. Taken together, the findings from in vitro and in vivo experiments provide new insights into the promotion of wound healing by GSP.

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.

Procyanidins: A promising anti-diabetic agent with potential benefits on glucose metabolism and diabetes complications.

Diabetes mellitus (DM) is a complex disease with alarming worldwide health implications and high mortality rates, largely due to its complications such as cardiovascular disease, nephropathy, neuropathy, and retinopathy. Recent research has shown that procyanidins (PC), a type of flavonoid, have strong antioxidant and free radical elimination effects, and may be useful in improving glucose metabolism, enhancing pancreatic islet cell activity, and decreasing the prevalence of DM complications. This review article presents a systematic search for peer-reviewed articles on the use of PC in the treatment of DM, without any language restrictions. The article also discusses the potential for PC to sensitise DM medications and improve their efficacy. Recent in vivo and in vitro studies have demonstrated promising results in improving the biological activity and bioavailability of PC for the treatment of DM. The article concludes by highlighting the potential for novel materials and targeted drug delivery methods to enhance the pharmacokinetics and bioactivity of PC, leading to the creation of safer and more effective anti-DM medications in the future.

Anti-inflammatory and antioxidant properties of Bertholletia excelsa(H.B.K) bark extract

Bertholletia excelsais native to the Amazon Rainforest and is popularly known as the Brazil nut. It has socioeconomic importance due its nuts being a great export product. There are fewstudies in the literature regarding the biotechnological potential of its bark, although it is used in folk medicine. The aim of this study was to determine the chemical constituents, anti-inflammatory and antioxidant properties of B. excelsabark extract(BEB). Twelve substances were identified by LC/MS/MS, and cytotoxicity tests were carried out, as well as analyses of nitric oxide production and elimination of free radicals. BEB caused cytoprotection against oxidative stress in macrophages, increased HMOX-1 expression, overcame the antioxidant effects of GPx-1 and reduced its expression and was able to inhibit leukocyte migration in use peritonitis. BEB efficiently attenuated oxidative stress due to its antioxidant and anti-inflammatory properties and, as such, can be used as a safe and effective source of a natural herbal medicine.

New insights into the antimicrobial action and protective therapeutic effect of tirapazamine towards Escherichia coli-infected mice

Escherichia coli is an important pathogen responsible for numerous cases of diarrhoea worldwide. The bioreductive agent tirapazamine (TPZ), which was clinically used to treat various types of cancers, has obvious antibacterial activity against E. coli strains. In the present study, we aimed to evaluate the protective therapeutic effects of TPZ in E. coli-infected mice and provide insights into its antimicrobial action mechanism. The MIC and MBC tests, drug sensitivity test, crystal violet assay and proteomic analysis were used to detect the in vitro antibacterial activity of TPZ. The clinical symptoms of infected mice, tissue bacteria load, histopathological features and gut microbiota changes were regarded as indicators to evaluation the efficacy of TPZ in vivo. Interestingly, TPZ-induced the reversal of drug resistance in E. coli by regulating the expression of resistance-related genes, which may have an auxiliary role in the clinical treatment of drug-resistant bacterial infections. More importantly, the proteomics analysis showed that TPZ upregulated 53 proteins and downregulated 47 proteins in E. coli. Among these, the bacterial defence response-related proteins colicin M and colicin B, SOS response-related proteins RecA, UvrABC system protein A, and Holliday junction ATP-dependent DNA helicase RuvB were all significantly upregulated. The quorum sensing-related protein glutamate decarboxylase, ABC transporter-related protein glycerol-3-phosphate transporter polar-binding protein, and ABC transporter polar-binding protein YtfQ were significantly downregulated. The oxidoreductase activity-related proteins pyridine nucleotide-disulfide oxidoreductase, glutaredoxin 2 (Grx2), NAD(+)-dependent aldehyde reductase, and acetaldehyde dehydrogenase, which participate in the elimination of harmful oxygen free radicals in the oxidation-reduction process pathway, were also significantly downregulated. Moreover, TPZ improved the survival rate of infected mice; significantly reduced the bacteria load in the liver, spleen, and colon; and alleviated E. coli-associated pathological damages. The gut microbiota also changed in TPZ-treated mice, and these genera were considerably differentiated: Candidatus Arthromitus, Eubacterium coprostanoligenes group, Prevotellaceae UCG-001, Actinospica, and Bifidobacterium. TPZ may represent an effective and promising lead molecule for the development of antimicrobial agents for the treatment of E. coli infections.

Antioxidant and Protective Effects of the Polyphenolic Glycoconjugate from Agrimonia eupatoria L. Herb in the Prevention of Inflammation in Human Cells

Herein, structural and biological studies of a complex biopolymer (polyphenolic glycoconjugate) isolated from the flowering parts of Agrimonia eupatoria L. (AE) are presented. Spectroscopic analyses (UV-Vis and 1H NMR) of the aglycone component of AE confirmed that it consists mainly of aromatic and aliphatic structures characteristic of polyphenols. AE showed significant free radical elimination activity, i.e., ABTS+ and DPPH·, and was an effective copper reducing agent in the CUPRAC test, eventually proving that AE is a powerful antioxidant. AE was nontoxic to human lung adenocarcinoma cells (A549) and mouse fibroblasts (L929) and was nongenotoxic to S. typhimurium bacterial strains TA98 and TA100. Moreover, AE did not induce the release of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) by human pulmonary vein (HPVE-26) endothelial cells or human peripheral blood mononuclear cells (PBMCs). These findings correlated with the low activation of the transcription factor NF-κB in these cells, which plays an important role in the regulation of the expression of genes responsible for inflammatory mediator synthesis. The AE properties described here suggest that it may be useful for protecting cells from the adverse consequences of oxidative stress and could be valuable as a biomaterial for surface functionalization.

Click-crosslinked in-situ hydrogel improves the therapeutic effect in wound infections through antibacterial, antioxidant and anti-inflammatory activities

Bacterial infection, free radical accumulation and excessive inflammation are major factors leading to delayed wound healing. The rapid and effective elimination of wound bacteria and excess free radicals, and modulation of the wound immune microenvironment to accelerate infected wound healing is one of the pressing clinical issues. Common wound dressing or drugs are single-functional and risk of developing drug resistance. Therefore, multifunctional biomaterials with accelerated wound healing are urgently desired. Herein, we reported a click-crosslinked hydrogel with antibacterial, antioxidant and anti-inflammatory properties for infected wound repair. The hydrogel gelated from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl chitosan based on “click” chemistry and Schiff base reaction possess short gelation time, good biocompatibility, broad-spectrum antibacterial activity, appropriate antioxidant and anti-inflammatory ability. Hydrogels effectively activate macrophage polarization toward the M2 phenotype and significantly promote the migration of repair-related cells (fibroblasts, epithelial cells and endothelial cells) and angiogenesis in vitro through paracrine mechanism. The in vivo results from a full-thickness infected wound model demonstrated that hydrogels can promote wound repair and regeneration by promoting angiogenesis and re-epithelialization through antibacterial, antioxidant and M2-type macrophage polarization. The bioactive hydrogels designed with antibacterial, antioxidant and M2 polarization promoting properties provide an efficient strategy for infected wound repair.