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Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cinnamic acids are aromatic acids primarily found in plants and plant-derived food. Phenolic cinnamic acids, with one or more hydroxyl groups in the aromatic ring, often contribute to the biological activities attributed to these compounds. The presence of hydroxyl groups and a carboxyl group makes cinnamic acids very hydrophilic, preventing them from crossing biological membranes and exerting their biological activities. To alleviate this condition, a panel of synthetic modifications have been made leading to a diverse set of phenolic cinnamic structures. In this review, an overview of the natural phenolic cinnamic acid derivatives and their plant sources (more than 200) is described. The synthetic approaches to obtain the referred derivatives (more than 200) namely esters and amides are reviewed. Further, their anti-inflammatory activity (more than 70 compounds) is scrutinized. Finally, future directions will be indicated to translate the research on phenolic cinnamic derivatives into potentially effective anti-inflammatory drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study investigated the changes in phytochemical composition and inflammatory response of crude papaya (Carica papaya L.) seed oil (CPO) and its refined forms (degummed, PDG; deacidified, PDA; decolorized, PDC; deodorized, PDO). Oils were analyzed for their phytochemical composition, oil quality parameters, antioxidant activity, and their inflammatory response in LPS-stimulated THP-1 macrophages. At higher refining degrees, particularly after deacidification, the contents of phytochemicals (sterols, tocopherols, and polyphenols) decreased while oxidation products increased. Both CPO (0.1-1.0 mg/mL) and PDG reduced the secretion and mRNA expression of LPS-stimulated inflammatory cytokines and mediators and also blocked the activation of the NF-κB pathway. PDA, PDC, and PDO showed low anti-inflammatory or even pro-inflammatory activity. Correlation analysis showed that 4 polyphenols and 2 phytosterols were responsible for the oil's anti-inflammatory effects. These findings indicated that moderate refining is suggested for papaya seed oil processing for retaining bioactive ingredients and anti-inflammatory ability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a pivotal role in producing pro-inflammatory eicosanoids, including prostaglandins (PGs) and leukotrienes (LTs), in the inflammation process. Mitragynine is a primary alkaloid contained in the kratom's leaves and has been reported to show anti-inflammatory activity by suppressing COX-2 mRNA translation to lowering PGs synthesis. In this study, the Kratom's alkaloid extract containing ~ 46% mitragynine was found to exhibit dual inhibition activity towards COX-2/5-LOX enzymes at concentrations below 25 ppm in the LPS-induced RAW 264.7 macrophage cells. At these levels, no cell toxicity was observed while the cells became death (e.g., 10-46% viability at 50-100 ppm) and only COX-2 inhibition activity was observed after exposed with more than 25 ppm of alkaloid extract. In contrast, the methanolic-crude extract of Kratom's leaf containing ~ 5% mitragynine showed no inhibition toward COX-2/5-LOX enzymes and did not toxic onto the cells, even after treated at 100 ppm. The alkaloid extract suppressed several antiinflammation parameters, including ROS (64% reduction at 25 ppm), NO (30% reduction at 25 ppm), TNF-α (~ 50% reduction at 25 ppm), and IL-6 production (60% reduction at 6.25 ppm). In silico molecular studies indicated strong binding affinity of Kratom alkaloids to COX-2 and 5-LOX active sites, supporting the Kratom's alkaloids to have great potential dual inhibition activity towards COX-2/5-LOX enzymes and to be developed as a safer NSAIDs with fewer side effects., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Fructus Choerospondiatis (FC) has been utilized in Mongolian medicine for the treatment of many diseases. This investigation assessed the coloration, five active components, total phenolic and flavonol contents, as well as the antioxidant and antibacterial properties of different parts of FC from eight cultivars, and the optimal cultivar was identified to determine the anti-inflammatory capacity of all parts. The findings revealed that L* and b* values of the dried peel powder were the highest and the a* value of whole fruit powder was the highest. The concentrations of gallic acid, catechin, epicatechin, total phenols, and total flavonoids exhibited a positive correlation with antioxidant activity. A comprehensive analysis revealed that the peel contained a greater abundance of active compounds and exhibited stronger antioxidant and antibacterial properties compared to other parts. RPNO.1 can be used as the source of high-quality FC for clinical application. In vivo anti-inflammatory experiments indicated that both the flesh and peel of RPNO.1 displayed the highest anti-inflammatory effect. This research not only addressed the gap in studies regarding FC ' s anti-inflammatory properties but also proved that the peel of FC, which was often discarded, had utilization value and could be used as a medicinal herb., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer's disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators. However, its clinical efficacy is hindered by poor solubility and bioavailability. Our study introduces the use of H-Ferritin nanocages (HFn) as a nanoformulation vehicle for Cur, aiming to enhance its therapeutic potential for AD. In this work, we characterized a nanoformulation of Cur in HFn (HFn-CUR) by evaluating its safety, stability, and its transport across the blood-brain barrier (BBB) in vitro. Moreover, we evaluated the efficacy of HFn-CUR by transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from both AD patients and healthy controls (HC), and by using the well-established 5xFAD mouse model of AD., Results: Our data show that HFn-CUR exhibits improved water dispersibility, is non-toxic, and can traverse the BBB. Regarding its activity on PBMCs from AD patients, HFn-CUR enhances cellular responses to inflammation and reduces RAGE-mediated stress. Studies on an AD mouse model demonstrate that HFn-CUR exhibits mild beneficial effects on cognitive performance. Moreover, it effectively reduces microgliosis and astrogliosis and in vivo in mouse, suggesting potential neuroprotective benefits., Conclusions: Our data suggest that HFn-CUR is safe and effective in reducing inflammation in both in vitro and in vivo models of AD, supporting the need for further experiments to define its optimal use., Competing Interests: Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards. The study design was examined by the IRBs of the enrolling institutions. The study protocol to obtain blood from patients was approved by the Ethical Committee of the IRCCS Mondino Foundation (Pavia, Italy) (Code: 20170001758). Informed consent was obtained from all subjects involved in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

CNS Drug discovery has been challenging due to the lack of clarity on CNS diseases' basic biological and pathological mechanisms. Despite the difficulty, some CNS drugs have been developed based on phenotypic effects. Herein, we propose a phenotype-structure relationship model, which predicts an anti-neuroinflammatory potency based on 3D molecular structures of the phenotype-active or inactive compounds without specifying targets. For this chemo-centric study, a predictive model of the nitric oxide (NO) inhibitory potency in hyper-activated microglia is built from the 548 agents, which were collected from 95 research articles (28 substructures consisting of natural products and synthetic scaffolds) and doubly externally validated by the agents of 9 research articles as third set. 3D Structures (multi-conformer ensemble) of every agent were encoded into the E3FP molecular fingerprint of the Keiser group as a 3D molecular representation. The location information of the molecular fingerprints could be learned and validated to classify the inhibitory potency of compounds (IC 50 cut-off between the active and inactive: 37.1 µM): (1) multi-layer perceptron (MLP) (AUC- CV : 0.997, AUC- Test : 0.992), (2) recurrent neural network (RNN) (AUC- CV : 0.999, AUC- Test : 0.995), and (3) convolutional neural network (CNN) (AUC- CV : 0.998, AUC- Test : 0.994). The high performance of these models was compared with that of four classical machine classification models (Logistic, Ridge, Lasso, and Naïve Bayes). We named the binary classification models NO-Classifier. Independent test set validation and decision region analysis of the independent test set doubly demonstrated NO-Classifier effectively discerned the anti-inflammatory potency of testing compounds in inflammatory cell phenotype with the webserver in https://no-classifier.onrender.com., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Constant efforts have been made to move towards maintaining the positive anti-inflammatory functions of glucocorticoids (GCs) while minimizing side effects. The anti-inflammatory effect of GCs is mainly attributed to the inhibition of major inflammatory pathways such as NF-κB through GR transrepression, while its side effects are mainly mediated by transactivation. Here, we investigated the selective glucocorticoid receptor modulator (SGRM)-like properties of a plant-derived compound. In this study, glucocorticoid receptor (GR)-mediated alleviation of inflammation by SP-8 was investigated by a combination of in vitro, in silico, and in vivo approaches. Molecular docking and cellular thermal shift assay suggested that SP-8 bound stably to the active site of GR via hydrogen bonding and hydrophobic interactions. SP-8 activated GR, induced GR nuclear translocation, and inhibited NF-κB pathway activation. Furthermore, SP-8 did not up-regulate the gene and protein expression of PEPCK and TAT in HepG2 cells, and it did not induce fat deposition like GC and has little effect on bone metabolism. Interestingly, SP-8 upregulated GR protein expression and did not cause GR phosphorylation at Ser211 in RAW264.7 cells. This work proved that SP-8 dissociated characteristics of transrepression and transactivation can be separated. In addition, the in vitro and in vivo anti-inflammatory effects of SP-8 were confirmed in LPS-induced RAW 264.7 cells and in a mouse model of DSS-induced ulcerative colitis, respectively. In conclusion, SP-8 might serve as a potential SGRM and might hold great potential for therapeutic use in inflammatory diseases., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We the undersigned declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We understand that the Corresponding Author is the sole contact for the Editorial process. She is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs., (Copyright © 2024. Published by Elsevier B.V.)

Eleven compounds including caffeic acid (CA), 4 kinds of caffeoylquinic acid (CQA) and 6 kinds of dicaffeoylquinic acid (DCQA), were selected to evaluate the anti-inflammatory effectiveness using mouse primary peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). The optimal non-cytotoxic doses of each individual compound were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines secreted by treated macrophages were analyzed using the enzyme-linked immunosorbent assay. Cytokine secretion profiles of each individual test sample at optimal non-cytotoxic doses were further analyzed using Principal Component Analysis (PCA). The results showed that CA and all selected CQAs exhibited lower cytotoxicity (IC 50 : >50 μmol/l). Both CA and 5-CQA were found to have the most significant contributions for inhibiting pro-inflammatory cytokines, but increasing anti-inflammatory cytokine secretions, evidencing that CA at 10 μmol/l and 5-CQA at 25 μmol/l can be qualified as potent anti-inflammatory agents for treating inflammation-related diseases., Competing Interests: Declaration of competing interest The authors declare that there is no known competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Plant vernacular names can provide clues about the popular use of a species in different regions and are valuable sources of information about the culture or vocabulary of a population. Several medicinal plants in Brazil have received names of medicines and brand-name products., Aim of the Study: The present work aimed to evaluate the chemical composition and pharmacological activity in the central nervous system of three species known popularly by brand names of analgesic, anti-inflammatory, antispasmodic, and digestive drugs., Materials and Methods: Hydroethanolic extracts of Alternanthera dentata (AD), Ocimum carnosum (OC), and Plectranthus barbatus (PB) aerial parts were submitted to phytochemical analysis by HPLC-PAD-ESI-MS/MS and evaluated in animal models at doses of 500 and 1000 mg/kg. Mice were tested on hot plate, acetic acid-induced writing, formalin-induced licking, and intestinal transit tests. Aspirin and morphine were employed as standard drugs., Results: The three extracts did not change the mice's response on the hot plate. Hydroethanolic extracts of AD and PB reduced the number of writhes and licking time, while OC was only effective on the licking test at dose of 1000 mg/kg. In addition, AD and OC reduced intestinal transit, while PB increased gut motility., Conclusions: Pharmacological tests supported some popular uses, suggesting peripheral antinociceptive and anti-inflammatory effects, while the phytochemical analysis showed the presence of several flavonoids in the three hydroethanolic extracts and steroids in PB, with some barbatusterol derivatives described for the first time in the species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In addition to their pigment properties, the potential health benefits of anthocyanins have made them a subject of interest in recent years. This study aimed to obtain purified anthocyanin fractions from native Mexican black bean cultivars using Amberlite XAD-7 resin column and HPCCC and evaluate their anti-inflammatory properties using RAW 264.7 cells. The major anthocyanins in the purified anthocyanin fractions were delphinidin 3-glucoside (61.8%), petunidin 3-glucoside (25.2%), and malvidin 3-glucoside (12.2%). Purified anthocyanin fractions at 12.5 μg/mL effectively prevented LPS-induced ERK1/ERK2 phosphorylation and reduced the protein expression of COX-2 and mRNA expression of iNOS. Results showed that purified anthocyanin fractions have the potential to modulate the inflammatory response by inhibiting the production of pro-inflammatory mediators through the ERK1/ERK2 and NF-κB pathways. This study suggests that anthocyanins from black beans could be used as a natural strategy to help modulate inflammation-associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis., Competing Interests: Declarations Ethics approval and consent to participate The animal experiments were approved by the Ethics Committee for Experimental Use of Animals of the Shanghai Jiao Tong University School of Medicine (approval code: #SYXK-2013-0050). Consent for publication All authors agree for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We developed two short helical antimicrobial peptides, HVF18-a3 and its d-enantiomer, HVF18-a3-d, derived from the thrombin C-terminal peptide HVF18. These peptides exhibit potent antimicrobial activity against various bacteria by compromising both the outer and inner membranes, with low hemolytic activity. They are stable in the presence of physiological salts and human serum, exhibiting a low potential for developing drug resistance and excellent antibiofilm activity against Gram-negative bacteria. HVF18-a3-d also neutralized lipopolysaccharide (LPS) through direct binding interactions and suppressed the production of inflammatory cytokines through the inflammatory signaling pathway mediated by Toll-like receptor 4 in RAW264.7 cells stimulated with LPS. Both pre- and post-treatment with HVF18-a3-d significantly protected mice against fatal septic shock induced by carbapenem resistant Acinetobacter baumannii . These findings suggest HVF18-a3 and HVF18-a3-d are promising candidates for developing antibiotics against Gram-negative sepsis.

Wound healing is a complex biological process that can trigger inflammation and oxidative stress and impair myofibrillogenesis and angiogenesis. Several advanced wound-dressing nanocomposite materials have been designed to address these issues. Here, we designed a new multifunctional styrene-ethylene-butylene-styrene/silver nanowire (SEBS/AgNWs)-based nanocomposite film with antimicrobial, antioxidant, and anti-inflammatory properties to promote wound healing. The porous morphological structure of SEBS/AgNWs enhances their antimicrobial, antioxidant, and anti-inflammatory properties. SEBS/AgNWs significantly inhibited the growth of Staphylococcus aureus , methicillin-resistant Staphylococcus aureus , and Escherichia coli strains, effectively wiping out ABTS•+, DPPH•, hydrogen peroxide (H 2 O 2 ), and hydroxyl (•OH) radicals, showing their effective ROS-scavenging properties. It further showed significant antioxidant properties by increasing the levels of enzyme-like catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), while decreasing malonaldehyde (MDA) levels. Additionally, SEBS/AgNWs reduced the expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), while increasing levels of transforming growth factor- β (TGF-β), vascular endothelial growth factor-A (VEGF), and CD31 in wound healing. This suggests that applying a multifunctional nanoplatform based on SEBS/AgNWs could enhance wound healing and improve patient outcomes in wound care management.

Background: Green synthesized nanoparticles have recently gained significant medicinal applications and oftentimes outperform their green sources. Selenium is of fundamental importance to human health, stemming from its distinctive physicochemical properties, such as antioxidant activity, inhibition of Lipid peroxidation, stabilization of membrane proteins, maintenance of membrane fluidity and modulation of cell signaling. Though reports have shown some therapeutic potential of Ackee plant parts such as antioxidant, anti-inflammatory, antimicrobial, neuroprotective, very few scientific proofs still exist in support of these effects., Methods: This study synthesized selenium nanoparticles (Se-NPs) from crude methanolic extracts of Ackee leaves (AKL) and Ackee arils (AKA), examined the photo-physical characteristics of the Se-NPs and determined the in-vitro antioxidant, antidiabetic, and anti-inflammatory potentials of AKL, AKA, and their Se-NPs using established protocols., Results: In both leaves and arils Se-NPs: UV spectroscopy revealed a qualitative absorbance at 310 nm; FTIR indicated multiple vibrations around 4000 cm -1 - 400 cm -1 ; SEM images of 5 µm principally showed consistent size distribution of amorphous and granular shape at a magnification of 10,000X; while EDS spectra strongly confirm the presence of atomic Se compound at 30 kV. Various antioxidant activities assays carried out showed a range of approximately 4 to 60 times higher activities of the AKL, AKA, and Se-NPs than Ascorbic acid-the standard drug used. Furthermore, appreciable activities of more than 50% were obtained for alpha-amylase and alpha-glucosidase inhibitory activities, along with highly significant activities of haemoglobin glycosylation, glucose uptake, membrane stabilization, anti-arthritic, anti-haemolysis activities, when AKL, AKA, and Se-NPs were compared with standard drugs., Conclusion: Encouraging the development and utilization of AKL, AKA, and Se-NPs will provide tremendous therapeutic efficacy and bioavailability approaches towards the management of diabetes, inflammation, and other oxidative stress-related diseases., (© 2024. The Author(s).)

Eleven new macrocyclic casbane-type diterpenes, namely sinueracasbanones E-O (1-11), have been isolated from the South China Sea soft coral Sinularia erecta using combined column chromatography. The structures of new compounds were elucidated by extensive spectroscopic data analysis, the modified Mosher's method, X-ray diffraction analysis and quantum mechanical calculation methods. In bioassay, compounds 2, 5, 10 and 11 displayed interesting anti-inflammatory activities by the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α protein release with half maximal inhibitory concentration (IC 50 ) values of 15.6, 7.1, 13.7 and 6.6 µM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Atorvastatin (ATV), a medication used to reduce cholesterol levels, possesses properties that can counteract the damaging effects of free radicals and reduce inflammation. However, the administration of ATV orally is associated with low systemic bioavailability due to its limited capacity to dissolve in water and significant first-pass effect. This study aimed to assess the appropriateness of employing nano-vesicles for transdermal administration of ATV in order to enhance its anti-inflammatory effects., Methods: ATV-loaded transethosomes (ATV-TEs) were optimized using the 3 3 Box-Behnken design. The ATV-TEs that were created were evaluated for their vesicle size, encapsulation efficiency (% EE), and percent release of drug. The optimum formulation was integrated into a hydroxypropyl methylcellulose (HPMC) emulsion-based gel (ATV-TEs emulgel) using jojoba oil. ATV-TEs emulgel was examined for its physical characteristics, ex vivo permeability, histological, and anti-inflammatory effect in a rat model of inflamed paw edema., Results: The optimized transethosomes exhibited a vesicle size of 158.00 nm and an encapsulation efficiency of 80.14 ± 1.42%. Furthermore, the use of transethosomal vesicles effectively prolonged the release of ATV for a duration of 24 hours, in contrast to the pure drug suspension. In addition, the transethosomal emulgel loaded with ATV exhibited a 3.8-fold increase in the transdermal flow of ATV, in comparison to the pure drug suspension. ATV-TEs emulgel demonstrated a strong anti-inflammatory impact in the carrageenan-induced paw edema model., Discussion: This was evident from the significant reduction in paw edema, which was equivalent to the effect of the standard anti-inflammatory medicine, Diclofenac sodium., Conclusion: In summary, transethosomes, as a whole, might potentially serve as an effective method for delivering drugs via the skin. This could improve the ability of ATV to reduce inflammation by increasing its absorption through the skin., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Abdallah et al.)

Emergency wounds are often accompanied by bacterial infection, oxidative stress, and excessive inflammation due to the inability to quickly close and stop bleeding, resulting in chronic wounds that are difficult to heal. Clinically, surgical suturing is the fastest method for wound closure, but it is only suitable for wounds with small bleeding volumes and causes unsightly scar formation. Consequently, there is a critical need for hemostatic dressings versatile enough to address a spectrum of diverse and intricate wounds, especially in emergency scenarios. In this study, we constructed a unique versatile natural gelatin-based hydrogel with hemostasis, antibacterial, and anti-inflammation properties. The hydrogel was composed of 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butyrylethylenediamine-modified methacrylated gelatin (GelMA-NB) and epigallocatechin gallate-grafted polylysine (EPL-EGCG), which imparts adhesion, antibacterial and antioxidant properties to the hydrogel. Simultaneously, the hydrogel was loaded with GelMA microspheres encapsulating natural resveratrol (RES@GM). This combination not only exhibited outstanding hemostatic capabilities but also preserved the anti-inflammatory potential of RES. In different animal models, the hydrogel exhibited outstanding hemostatic and wound healing effects, down-regulated the expression of IL-1 β to promote inflammatory regulation and potential for angiogenesis and anti-scar. In conclusion, unique versatile natural gelatin-based hydrogel suitable for various complex wounds provides a promising strategy for emergency wound dressing applications., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability., Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability., Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis., Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro., Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis., Competing Interests: The authors declare no conflict of interest., (© 2024 Fu et al.)

Fermenting edible filamentous fungi with food industry by-products, such as young apples, shows promise for producing mycoproteins and functional peptides. This study aimed to evaluate the production of mycoprotein by fermenting different edible-grade filamentous fungi using young apples as a substrate. Schizophyllum commune DS1 (DS1) demonstrated significant potential for generating mycoprotein, yielding 33.56 ± 0.82 %. From the hydrolysis of DS1 mycoprotein, three polypeptides were identified with the capacity of inhibiting nitric oxide synthase (iNOS): DNIQGITKPAIR (DR12), SDNAFGGR (SR8), and ASDPSGF (AF7). Computational analysis, including bioinformatics and molecular docking, indicated their high affinity for inhibiting iNOS, with binding energies of -452.8157 kcal/mol, -388.0222 kcal/mol, and -323.8843 kcal/mol, respectively. This binding was facilitated through various interactions such as electrostatic forces, π-π interactions, hydrogen bonds, and non-covalent interactions, resulting in potential anti-inflammatory properties. Furthermore, cell experiments using RAW264.7 macrophages demonstrated that these peptides effectively suppressed nitric oxide production in a dose-dependent manner. Additionally, they reduced the production of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β), inducible iNOS, and cell apoptosis. In conclusion, this study presents a novel approach for developing plant-based mycoproteins and a new source for discovering food-derived bioactive peptides., Competing Interests: Declaration of competing interest The authors assert that they have no identifiable conflicting financial interests or personal relationships that might have influenced the findings reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Oxidative stress, inflammation, and bacterial infection are critical barriers to wound healing. In this work, a composite wound dressing was designed to promote wound healing and reduce complications. A hydrogel with antibacterial, anti-inflammatory, and antioxidant properties was prepared by crosslinking chitosan (CS) and oxidized konjac glucomannan with Mg 2+ . We named the prepared hydrogel CPO/Mg 2+ . The proposed hydrogel demonstrated a significant capacity for promoting wound healing. Experimental results indicate that the CPO/Mg 2+ composite hydrogel exhibits a bacteriostatic rate of over 95 % against S. aureus and P. aeruginosa. Furthermore, CPO/Mg 2+ reduced oxidative damage to L929 cells in an H 2 O 2 -induced ROS microenvironment and promoted the polarization of macrophage M2. In vivo full-thickness skin defect experiments revealed that the CPO/Mg 2+ composite hydrogel enhances collagen deposition and angiogenesis, achieving a closure rate of over 95 % for infected wounds within 14 days. This novel composite hydrogel offers an effective strategy for the repair of infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammation and reactive oxygen species (ROS) production often accompany the repair of severe skin wounds, and the management of wounds has always been a clinical challenge, so the design of a hydrogel wound dressing with antioxidant and anti-inflammatory properties is of significant importance. This work incorporated strontium ranelate (SrR) into the keratin/hyaluronic acid (K/HA) hydrogel, which could scavenge ROS and reduce inflammation. The optimized hydrogel exhibits large pore size (217.2 μm), high porosity (57 %), high swelling rate (1759.52 %), and an elastic modulus (3.41 kPa). In the in vitro study, incorporating SrR into hydrogel effectively inhibited oxidative damage in mouse fibroblasts (L929) and improved anti-inflammatory effect in RAW264.7 cells stimulated by lipopolysaccharide. The in vivo study showed that, compared with the control group, the expression of ROS, IL-6 and TNF - α in the K/HA/0.5 mM SrR group were significantly reduced to 31.6 %, 39.7 % and 61.1 %, respectively. The in vivo evaluation in a full-thickness wound defect model demonstrated that K/HA/0.5 mM SrR hydrogel promotes wound healing by attenuating ROS levels, reducing inflammation, and promoting microangiogenesis. In summary, the excellent ROS scavenging and anti-inflammatory properties of SrR make the K/HA/SrR hydrogel a promising and effective strategy for wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A miscellaneous polysaccharide, PAP55-3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55-3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55-3-1 can effectively inhibit reactive oxygen species (ROS) and O 2 - production following H 2 O 2 - induction. After H 2 O 2 - induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55-3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H 2 O 2 -induced mitochondrial oxidative damage. Additionally, PAP55-3-1 inhibited the M1 polarization of macrophages stimulated by H 2 O 2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55-3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55-3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities., Competing Interests: Declaration of competing interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

We investigated the antioxidant and anti-inflammatory properties of Lacticaseibacillus rhamnosus Ram12-derived EPSRam12 in a D-galactose-induced liver injury mouse model. Initially, EPSRam12 was characterized for its composition, molecular weight, and structural features. It was then administered orally to D-galactose-induced mice (which had received an intraperitoneal injection of D-galactose, 100 mg/kg body weight) at doses of 25 mg/kg (low dose) and 50 mg/kg (high dose) for 45 days. After treatment, biochemical markers, antioxidant status, cytokine levels, and liver inflammatory gene expression were evaluated. The results showed that EPSRam12 was a branched chain heteropolysaccharide comprising mannose, rhamnose, and arabinose monosaccharides with molecular weight of 2.6 million Daltons. EPSRam12, with its unique structural features such as hydroxyl and methyl groups, glycosidic bonds, and functional groups like carboxylates and sulfates, demonstrated promising bioactive properties. Administering EPSRam12 to D-galactose-induced mice resulted in a significant increase in antioxidant enzyme activity and a reduction in oxidative stress indicators. Additionally, it exhibited anti-inflammatory effects by modulating cytokine levels, lowering pro-inflammatory markers, and inhibiting key inflammatory pathways in the liver in a dose-dependent manner. Our findings underscore the potential of EPSRam12 as an effective antioxidant and anti-inflammatory agent, with promising applications in functional foods and pharmaceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and other immunosuppressants are commonly used medications for treating inflammation. However, these drugs often come with numerous side effects. Therefore, finding more effective methods for inflammation treatment has become more necessary. The study of anti-inflammatory peptides can effectively address these issues. In this work, we propose a contextual self-attention deep learning model, coupled with features extracted from a pre-trained protein language model, to predict Anti-inflammatory Peptides (AIP). The contextual self-attention module can effectively enhance and learn the features extracted from the pre-trained protein language model, resulting in high accuracy to predict AIP. Additionally, we compared the performance of features extracted from popular pre-trained protein language models available in the market. Finally, Prot-T5 features demonstrated the best comprehensive performance as the input for our deep learning model named DeepAIP. Compared with existing methods on benchmark test dataset, DeepAIP gets higher Matthews Correlation Coefficient and Accuracy score than the second-best method by 16.35 % and 6.91 %, respectively. Performance comparison analysis was conducted using a dataset of 17 novel anti-inflammatory peptide sequences. DeepAIP demonstrates outstanding accuracy, correctly identifying all 17 peptide types as AIP and predicting values closer to the true ones. Data and code are available at https://github.com/YangQingGuoCCZU/DeepAIP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photoaging induced by ultraviolet (UV) results in oxidative stress and inflammation. Noble metal nanozymes have strong antioxidant and anti-inflammatory capacity, which are expected to eliminate the excessive reactive oxygen species (ROS) and inflammatory factors in the photoaged skin. Hence, we have synthesized ultrasmall platinum nanoparticles coated with polyvinylpyrrolidone (Pt NPs) with a diameter of nearly 5 nm for photoaging treatment. Thanks to multi-enzymatic capacities (catalase, peroxidase, and superoxide dismutase) of Pt NPs, they can effectively protect fibroblasts from UV-induced ROS attack, relieve fibroblasts from UV-induced cell cycle arrest, downregulate matrix metalloproteinases (MMPs) to regenerate type I collagen, and inhibit M1 macrophage polarization to decrease the expression of inflammatory factors. For photoaged mice treatment, we employ the concept of routine spray skincare and encapsulate Pt NPs solution in a spray bottle. In combination with roller needle, following Pt NPs nano-enzymatic spray given, UV-induced photoaged mice display reduced wrinkle formation in the collagen-depleted dermal tissue of mice and more youthful performance in both appearance and organizational structure. Consequently, multi-enzymatic functions of Pt NPs nano-spray offers a promising avenue for anti-photoaging therapy, providing potential benefits in both preventative and restorative skincare applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sulfated polysaccharides (SPSs) have excellent physicochemical properties, attracting research interest in the pharmaceutical industry. A previous study extracted SPS (named Suc40) from the edible fungus, Poria cocos and demonstrated that it exhibited anti-inflammatory and anticancer activities. In this study, three fractions of Suc40, Suc40 F1, Suc40 F2, and Suc40 F3, with different molecular weights and sulfate contents were prepared through gel-filtration column chromatography. The molecular weights of F1, F2, and F3 were approximately 616.23, 82.57, and 6.21 kDa, respectively, and their sulfate content were 0.23, 1.65, and 1.90 mmol/g, respectively. The fractions' anti-inflammatory activities were determined by assessing their ability to suppress inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Suc40 F2 and Suc40 F3 suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production by 60 % and 35 %, respectively. Suc40 F2 and Suc40 F3 suppressed protein kinase B (AKT)/p38 and p38 signaling, which resulted in anti-inflammatory effects. The fractions' anti-lung cancer activity was evaluated by assessing their H1975 cell proliferation inhibition. Suc40 F3 at a concentration of 800 μg/ml exhibited maximal cell proliferation inhibition. The low molecular weight and high sulfate content of Suc40 F3 were associated with its enhanced anti-inflammatory and anti-lung cancer activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fungal keratitis (FK) is recognized as a stubborn ocular condition, caused by intense fungal invasiveness and heightened immune reaction. The glycosaminoglycan chondroitin sulfate exhibits properties of immunomodulation and tissue regeneration. In prior investigations, oxidized chondroitin sulfate (OCS) ameliorated the prognosis of FK in murine models. To further improve the curative efficacy, we used the antifungal drug natamycin to functionalize OCS and prepared oxidized chondroitin sulfate-natamycin (ON) eye drops. The structure of ON was characterized by FTIR, UV-vis, and XPS, revealing that the amino group of natamycin combined with the aldehyde group in OCS through Schiff base reaction. Antifungal experiments revealed that ON inhibited fungal growth and disrupted the mycelium structure. ON exhibited exceptional biocompatibility and promoted the proliferation of corneal epithelial cells. Pharmacokinetic analysis indicated that ON enhanced drug utilization by extending the mean residence time in tears. In murine FK, ON treatment reduced the clinical score and corneal fungal load, restored corneal stroma conformation, and facilitated epithelial repair. ON effectively inhibited neutrophil infiltration and decreased the expression of TLR-4, LOX-1, IL-1β, and TNF-α. Our research demonstrated that ON eye drops achieved multifunctional treatment for FK, including inhibiting fungal growth, promoting corneal repair, enhancing drug bioavailability, and controlling inflammatory reactions., Competing Interests: Declaration of competing interest This work was supported by the National Natural Science Foundation of China (No. 82171029, No. 82101095). The authors declare that they have no known competing financial interets or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which there is currently no efficacious therapeutic drug with fewer side effects. Therefore, the development of approaches for the prevention of UC from natural food sources is urgently needed. In this study, mice were pre-fed with sea cucumber peptides prior to dextran sodium sulfate (DSS) induction. Results showed that sea cucumber peptides decreased pro-inflammatory cytokine (IL-4 and IL-10) levels and remissions of main clinic symptoms in a dose-dependent manner. The composition of peptides was identified, and the anti-inflammatory molecular mechanism was evaluated by silico prediction. The molecular weight of the peptides was 243-1800 Da and composed of 3-18 amino acid residues. Online activity assessment and molecular docking prediction revealed that tripeptides of FGI, FLI, FLL, GFL, GFM, IGF and LDF exhibited strong anti-inflammatory activity. Particularly, LDF showed the highest potency, with a binding energy of -5.37 kJ/mol. Network pharmacology analysis of UC related diseases indicated that active peptides interact with colitis disease targets, primarily proto-oncogene tyrosine-protein kinase Src (SRC), E3 ubiquitin-protein ligase XIAP (XIAP) and angiotensin-converting enzyme (ACE). The results suggest that sea cucumber peptides have potential as a novel nutraceutical option for colitis relief., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Calotropis gigantea essential oil is utilized in outmoded medicine, therapeutics, and the cosmetic industries. However, the extreme volatility, oxidation susceptibility, and instability of this oil restricts its application. Thus, encapsulation is a more effective method of shielding this oil from unfavorable circumstances. The creation of oil/water (O/W) nanoemulsions based on Calotropis gigantea essential oil (CEO), known as CNE ( Calotropis gigantea essential oil nanoemulsions), and an assessment of its biological potential were the goals of this work. UV, fluorescence, and FT-IR methods were used for physiological characterization. Biological activities, including anti-inflammatory, anti-diabetic, and anti-cancer effects. Studies on the pharmacokinetics of CNE were conducted. CNEs encapsulation efficiency was found to be 92%. The CNE nanoemulsions had a spherical shape with polydispersity index of 0.531, size of 200 nm, and a zeta potential of -35.9 mV. Even after being stored at various temperatures for 50 days, CNE nanoemulsions remained stable. Numerous tests were used to determine the antioxidant capacity of CNE, and the following IC50 values (µl/mL) were found: iron chelating assay: 18, hydroxyl radical scavenging: 37, and nitric oxide radical scavenging activity: 58. The percentage of HeLa cells that remained viable after being treated with CNE was 41% at a higher dose of 1 µl. CNE inhibited α-amylase in a dose-dependent manner, with 72% inhibition at its higher dose of 250 µL. Research on the kinetics of drugs showed that nanoemulsions showed Higuchi pattern. This research showed potential use of Calotropis gigantea oil-based nanoemulsions in the food, cosmetic, and pharmaceutical industries.

Effective wound care remains a significant challenge due to the need for infection prevention, inflammation reduction, and minimal tissue damage during dressing changes. To tackle these issues, we have developed a multifunctional hydrogel (CHI/CPBA/RU), composed of chitosan (CHI) modified with 4-carboxyphenylboronic acid (CPBA) and the natural flavonoid, rutin (RU). This design endows the hydrogel with body temperature-responsive adhesion and low temperature-triggered detachment, thus enabling painless removal during dressing changes. The CHI/CPBA/RU hydrogels exhibit excellent biocompatibility, maintaining over 97 % viability of L929 cells. They also demonstrate potent intracellular free radical scavenging activity, with scavenging ratios ranging from 53 % to 70 %. Additionally, these hydrogels show anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6, and iNOS) and increasing anti-inflammatory markers (Arg1 and CD206) in RAW 264.7 macrophages. Notably, they possess robust antimicrobial properties, inhibiting over 99.9 % of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth. In vivo testing on a murine full-thickness skin defect model shows that the hydrogel significantly accelerates wound healing by reducing inflammation, increasing collagen deposition, and promoting angiogenesis, achieving 98 % healing by day 10 compared to 78 % in the control group. These attributes make the polysaccharide-based hydrogel a promising material for advanced wound care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties., Results: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL -1 ), interleukin-6 (1.06 ng mL -1 ) and tumor necrosis factor-α (4440.45 ng mL -1 ). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL -1 ; superoxide dismutase: 0.589 μg mL -1 ) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL -1 )., Conclusion: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

A bioassay-guided isolation from Atractylodes lancea (Thunb.) DC. obtained 22 compounds, including eight previously undescribed sesquiterpenoids and polyacetylenes (1, 3 and 12-17), as well as fourteen known analogues, and their structures were confirmed by extensive spectroscopic methods. This study evaluated their antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) for the first time, as well as anti-inflammatory activity. Most of them, including new compounds, showed varying degrees of antibacterial activity against S. aureus and MRSA. Notably, compound 21 exhibited significant antibacterial activity against four different bacteria (MIC 6.25-20.00 μg/mL). This suggested that 21 may have the potential to be developed into a broad-spectrum antibacterial agent. Moreover, except for 9 and 11, most compounds exhibited great anti-inflammatory activity (IC 50 1.92-37.91 μM), and iNOS might be a potential target of these compounds according to the molecular docking analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Genus Asparagus is well known for its pharmacological activities and ethnopharmacological applications. In folk medicine, it is used in the management of several diseases such as diabetes, inflammations, and rheumatism. This work aimed to investigate the potential of Asparagus densiflorus meyeri root & aerial parts extracts as cytotoxic and anti-inflammatory and the investigation of their chemical profile. GC analysis & Folin-Ciocalteu and gravimetric methods were used respectively to estimate the lipoidal, phenolic, and saponin contents. MTT assay was conducted using two cell lines (MCF-7 & HepG2) to investigate the cytotoxic and anti-inflammatory activity using TNF-α stimulated MCF-7 cells through monitoring the level of nitric oxide release and NF-κB gene expression. Preliminary phytochemical investigation indicated that both extracted parts are equally rich in saponins, flavonoids, carbohydrates and/or glycosides, and sterols and/or triterpenes. Palmitic acid and β sitosterol represented the major saturated fatty acids and sterol, respectively. A significant cytotoxic activity against MCF-7 cells was recorded for DCM extract (IC 50 26.13 μg/ml). All tested extracts showed a significant decrease in NO release and NF-κB gene expression thus it possesses a potential anti-inflammatory activity. A. densiflorus meyeri is considered a good candidate as a food supplement for protection from malignancy., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The overexpression of inflammatory factors is closely related to the pathogenesis of acute kidney injury (AKI). Additionally, the overproduction of reactive oxygen species (ROS) further exacerbates the inflammatory response. In light of this, monotherapies focused solely on inflammation have proven to be suboptimal. Therefore, this study successfully developed a nanoparticle (SC@Se/GA) that possesses anti-inflammatory and antioxidant properties. The SC@Se/GA has a smaller size, better stability, and kidney-targeting. In vivo experiments showed that the GPx enzyme activity of SC@Se/GA increases by almost 50 % more than SC@Se alone, indicating its efficient ability to scavenge ROS. In the meantime, SC@Se/GA has a longer renal retention period (>24 h) than free drug GA, which can dramatically lower the levels of inflammatory factors TNF-α and IL-6. In summary, SC@Se/GA, through its synergistic anti-inflammatory and antioxidant effects, markedly alleviates CDDP-induced renal injury and restores renal function, providing a new effective strategy for treating AKI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Although chitooligosaccharides (COS) improve the drawbacks of chitosan, their biological activities in medical applications have not been highly appreciated. The main approach is to synthesise the COS derivatives in order to improve the biological properties of the COS. In this study, ferulic acid (FA) grafted onto COS (FA-COS) were synthesised and their mechanism of anti-inflammatory activity was investigated in the murine macrophage cells. The synthesis conditions of FA-COS were optimised and confirmed that the FA was successfully conjugated onto COS with the grafting effect of 15-34%. FA-COS exhibited anti-inflammatory activities via suppressing of nitric oxide formation, reducing iNOS expression at transcription and translation levels, down-regulation of TNF-α, IL-6 and IL-1 β genes; NF-κB and MAPKs signalling pathways. These results show anti-inflammatory molecular mechanism of FA-COS that exhibit enormous potential for prevention of inflammatory diseases.

To explore the new mode of action and reduce side effects, making conjugates of existing drugs is becoming an attractive tool in the realm of medicinal chemistry. In this work, we exploited this approach and synthesized new conjugates to assess their activities against the enzymes involved in different pathological conditions. Specifically, we design and synthesized conjugates involving acetylsalicylic acid and sulfa drugs, validating the newly crafted conjugates using techniques like IR, 1 HNMR, 13 CNMR, and elemental analysis. These conjugates underwent assessment for their ability to inhibit cyclooxygenase-2 (COX-2), urease enzymes, and their anti-inflammatory potential. A competitive mode of urease inhibition was observed for acetylsalicylic acid conjugated with sulfanilamide, sulfacetamide, and sulfadiazine with IC 50 of 2.49 ± 0.35 µM, 6.21 ± 0.28 µM, and 6.57 ± 0.44 µM, respectively. Remarkably, the acetylsalicylic acid-sulfamethoxazole conjugate exhibited exceptional anti-inflammatory activity, effectively curtailing induced edema by 83.7%, a result akin to the reference anti-inflammatory drug indomethacin's performance (86.8%). Additionally, it demonstrated comparable COX-2 inhibition (75.8%) to the reference selective COX-2 inhibitor celecoxib that exhibited 77.1% inhibition at 10 µM concentration. To deepen our understanding, we employed molecular docking techniques to predict the binding interactions of competitive inhibitors with COX-2 and urease receptors. Additionally, MD simulations were carried out, confirming the stability of inhibitor-target complexes throughout the simulation period, devoid of significant conformational changes. Collectively, our research underscores the potential of coupling approved medicinal compounds to usher in novel categories of pharmacological agents, holding promise for addressing a wide spectrum of pathological disorders involving COX-2 and urease enzymes.Communicated by Ramaswamy H. Sarma.

Bacopa monnieri (L.) Wettst (Plantaginaceae), is traditionally used in many countries as neural tonic and memory enhancer, or to relieve acute pain and inflammation. This study described the isolation and identification of one new, bacomoside D 3 ( 1 ), and seven known phenyl glycosides ( 2  -  8 ). The structures of isolates were established by analysis of their spectroscopic data or hydrolysis followed by HPLC analysis together with a comparison to those reported in the literature. These compounds were evaluated for antioxidant and anti-inflammatory activities. Among them, compounds 4 and 5 exhibited strong DPPH radical scavenging activity with IC 50 values of 9.77 ± 0.08 and 3.50 ± 0.04 µM, respectively. Compounds 2 and 5 significantly inhibited TNF- α production in LPS-stimulated RAW264.7 cells with IC 50 values of 40.60 ± 3.05 and 38.19 ± 1.75 µM, respectively. Furthermore, the active compounds could be efficient inhibitors of oxidants by interfering with the DPPH activity in silico study.

Microalgae are considered promising sustainable sources of natural bioactive compounds to be used in biotechnological sectors. In recent years, attention is increasingly given to the search of microalgae-derived compounds with antioxidant and anti-inflammatory properties for nutraceutical or pharmacological issues. In this context, attention is usually focused on the composition and bioactivity of algae or their extracts, while less interest is driven to their biological features, for example, those related to morphology and cultivation conditions. In addition, specific studies on the antioxidant and anti-inflammatory properties of microalgae mainly concern Chlorella or Spirulina. The present work was focused on the characterization of the Chlorophyta Neochloris oleoabundans under two combinations of cultivation modes: autotrophy and glucose-induced mixotrophy, each followed by starvation. Biomass for morphological and biochemical characterization, as well as for extract preparation, was harvested at the end of each cultivation phase. Analyses indicated a different content of the most important classes of bioactive compounds with antioxidant/anti-inflammatory properties (lipids, exo-polysaccharides, pigments, total phenolics, and proteins). In particular, the most promising condition able to prompt the production of antioxidant algal biomass with anti-inflammatory properties was the mixotrophic one. Under mixotrophy, beside an elevated algal biomass production, a strong photosynthetic metabolism with high appression of thylakoid membranes and characteristics of high photo-protection from oxidative damage was observed and linked to the overproduction of exo-polysaccharides and lipids rather than pigments. Overall, mixotrophy appears a good choice to produce natural bioactive extracts, potentially well tolerated by human metabolism and environmentally sustainable., (© 2024. The Author(s).)

Fabricating injectable hydrogel with multiple functions and effective promotion of wound repair has a great prospect in treatment of bacterial infected wounds. Herein, a pH/reactive oxygen species (ROS) dual responsive injectable hydrogel (PVBDL-gel) was constructed, the PVBDL-gel was cross-linked by dynamic Schiff base bonds and borate ester bonds between poly(vanillin acrylate-co-3 acrylamide phenylboronic acid-co-N,N-dimethylacrylamide) (P(VA-co-AAPBA-co-DMA)), oligolysines and polyvinyl alcohol (PVA). The anti-inflammatory drug, dexamethasone sodium phosphate (DEX), was encapsulated in this hydrogel. The hydrogel exhibited excellent degradability, stable rheology and suitable tissue adhesion, more importantly, which showing pH/ROS responsive ability and controllable releasing of DEX. In vitro and in vivo experiment results showed that the PVBDL-gel with good biocompatibility and efficient anti-infection ability can effectively eradicate 99.9 % of pathogenic bacteria within 3 h and promote the repair and regeneration of bacterial infection wounds. This novel multifunctional injectable hydrogel has great application in the field of bacterial infection wound repair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Piper sintenense Hatusima (PsH) is a member of the Piper genus used as food and folk medicine in China. However, the detailed chemical ingredients and potential pharmacological effects are still underexploited. In this study, we evaluated the anti-inflammatory and antigouty arthritis effect of the ethanolic extract of P. sintenense . Active compounds were isolated from the petroleum ether fraction resulting in six novel amide alkaloids ( 1 - 6 ) and 13 known analogues ( 7 - 19 ). All of the compounds exhibited excellent anti-inflammatory activities. Bioinformatics analysis and in vitro experiments showed that compound 4 had anti-inflammatory properties (IC 50 = 4.86 ± 0.32 μM) and antigouty arthritis activity. Mechanistic studies revealed that compound 4 exerted its favorable efficacy by regulating macrophage polarization by inhibiting P-STAT1/4. These findings provide new insights into the chemical composition and function of P. sintenense and expand its promising application as a functional food in the prevention and treatment of gouty arthritis.

Ethnopharmacological Relevance: Dendrobium crepidatum Lindl. ex Paxton is a perennial epiphyte of Dendrobium genus, distributed in southern China, and utilized as the traditional Chinese medicine "Shihu" in Yunnan Province. Due to its heat-clearing and detoxicating properties, it is formulated as the "XiaoCuoWan" as recorded in the China Pharmacopoeia, and specially used to treat chronic skin inflammatory diseases, such as acne., Aim of the Study: This research aimed to estimate impact of the octahydroindoline alkaloid Homocrepidine A (HCA), isolated from D. crepidatum, on acne inflammation using both human THP-1 cells and mouse models. Furthermore, the potential anti-inflammatory mechanism of HCA has been analyzed through molecular biology methods and computer simulation., Materials and Methods: THP-1 cells and mouse models induced by live Propionibacterium acnes (P. acnes) were employed to evaluate the anti-inflammatory properties of crude extract of D. crepidatum (DCE) and HCA. ELISA was utilized to detect the release of inflammatory cytokines in both cellular and murine ear tissues. RNAseq was used to screen the pathways associated with HCA-mediated inflammatory inhibition, while Western blot, RT-qPCR, and immunofluorescence were utilized to detect the expression of relevant proteins. Additionally, molecular docking simulations and cellular thermal shift assays were employed to confirm the target of HCA., Results: Our research shows that DCE and HCA can effectively alleviate acne inflammation. HCA inhibits TLR2 expression by interacting with amino acid residues in the TIR domain of hTLR2, including Pro-681, Asn-688, Trp-684, and Ile-685. Moreover, HCA disrupts inflammatory signal transduction mediated by MAPK and NF-κB pathways through MyD88-dependent pathway. Additionally, HCA treatment facilitates Nrf2 nuclear translocation and upregulates HO-1 expression, thereby inhibiting NLRP3 inflammasomes activation. In vivo experiments further revealed that HCA markedly attenuated erythema and swelling caused by P. acnes in mice ears, while also decreasing the expression of pro-inflammatory cytokines IL-1β and IL-8., Conclusions: Our research highlights the protective effects of D. crepidatum and its bioactive compound HCA against acne inflammation, marking the first exploration of its potential in this context. The discoveries indicate that HCA treatment may represent a promising functional approach for acne therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Rhapontici Radix ethanol extract (RRE) is derived from the dried root of Rhaponticum uniflorum (L.) DC belonging to the Asteraceae family. RRE exhibits significant anti-inflammatory and antioxidant properties; however, the potential of RRE in mastitis treatment requires further investigation., Aim of This Study: This research was performed to examine the protective properties of RRE against mastitis and the mechanisms underlying the effects of RRE., Material and Methods: RRE components were analyzed by HPLC-MS/MS and DPPH methods. Isochlorogenic acid B (ICAB) was obtained commercially. MTT assay was utilized to assess RRE or ICAB cytotoxicity in bovine mammary alveolar (MAC-T) cells. Immunohistochemistry were used to investigate the pathological alterations in mammary tissue. The protein levels of inflammatory cytokines and mediators were analyzed using ELISA, and the expression of MAPK and NF-κB signaling pathways, as well as p65 nuclear translocation, were analyzed through Western blotting and immunofluorescence techniques, respectively. Target proteins of RRE were screened by RNA-seq and tandem mass tag analyses. Protein interaction was revealed and confirmed using co-immunoprecipitation and CRISPR/Cas9-based knockdown and overexpression of target genes., Results: ICAB was revealed as one of the main components in RRE, and it was responsible for 84.33% of RRE radical scavenging activity. Both RRE and ICAB mitigated the infiltration of T lymphocytes in the mammary glands of mice, leading to decreased levels of inflammatory mediators (COX-2 and iNOS) and cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide (LPS)-induced MAC-T cells. Furthermore, RRE and ICAB suppressed the LPS-induced phosphorylation of NF-κB inhibitor and p65, thereby impeding p65 nuclear translocation in mouse mammary glands and MAC-T cells. In addition, RRE and ICAB attenuated the LPS-triggered activation of c-Jun N-terminal kinase 1/2, p38, and extracellular regulated protein kinase 1/2. Importantly, co-treated with LPS and ICAB in MAC-T cells, an upregulation of G-protein coupled receptor 161 (GPR161) and transmembrane protein 59 (TMEM59) was observed; the interact between TMEM59 and was found, leading to inhibition of NF-κB activity and inflammatory cytokine production., Conclusion: ICAB is a prominent antioxidant in RRE. RRE and ICAB reduce mammary inflammation via MAPK and NF-κB pathways and the interaction between TMEM59 and GPR161 mediates the control of ICAB in NF-κB signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ficus erecta, a traditional Chinese She Ethnomedicine, has been historically utilized to treat various inflammatory conditions such as arthritis, nephritis, and osteoporosis. However, the underlying mechanisms accounting for its anti-inflammatory activity, as well as its active components, largely remain elusive., Aim of the Study: The purpose of this research was to investigate the chemical constituents of F. erecta that contribute to its anti-inflammatory effects., Materials and Methods: Coumarins and flavones were obtained from the 95% EtOH extract of F. erecta using virous column chromatography and reversed-phase semipreparative HPLC. The structures of the new compounds were elucidated by extensive analysis of spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra, and CD experiments. Cultured macrophage RAW264.7 cells were utilized for the anti-inflammatory experiments. MTT cell viability assay, Griess reagent method, ELISA, and Western blot experiments were employed to evaluate the anti-inflammatory activity and investigate the related mechanism., Results: Four new (1-4) and eleven previously identified (5-16) coumarins, together with one new (17) and six known flavones (18-23) were isolated from the whole plant of F. erecta. Compounds 7 and 17 significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE 2 ) production without cytotoxic effects. Furthermore, compounds 7 and 17 reduced the production of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in a concentration-dependent manner. Western blot analysis indicated that compounds 7 and 17 suppressed the expression of iNOS, COX-2, and p-IκBα in LPS-stimulated RAW264.7 macrophage cells., Conclusion: The current phytochemical investigations revealed that coumarins and flavones represent the primary chemical constituents of F. erecta. Compounds 7 and 17 exhibit potent anti-inflammatory properties, linked with the inhibition of NF-κB activation by preventing the degradation of IκBα phosphorylation. These compounds may serve as promising candidates for treating or preventing certain inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ocimum basilicum is a valuable plant widely consumed worldwide and considered a rich source of polyphenols. This study examined the impact of the polyphenolic fraction isolated from basil (ObF) on human normal colon epithelial cells and human colorectal adenocarcinoma cells, evaluating its anti-inflammatory and protective activity against oxidative stress. The phytochemical characterization of the fraction was performed using ultra-performance liquid chromatography (UPLC) with a photodiode detector (DAD) and mass spectrometry (MS). UPLC-DAD-MS revealed that ObF predominantly contains caffeic acid derivatives, with rosmarinic acid and chicoric acid being the most abundant. The fraction demonstrated high antioxidant potential, as shown by DPPH assays, along with significant reducing power (FRAP). Furthermore, it prevented the depletion of antioxidant enzymes, including superoxide dismutase and catalase, and decreased malonylodialdehyde (MDA) in induced oxidative stress condition. Additionally, it exhibited a significant protective effect against H 2 O 2 -induced cytotoxicity in human normal colon epithelial cells. Although it had no impact on the viability of adenocarcinoma cells, it significantly reduced IL-1β levels in the neoplastic microenvironment. Our study demonstrated that basil polyphenols provide significant health benefits due to their antioxidant and protective activities.

Background: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence., Methods: In this study, Gd 3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs' anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer., Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd 3+ ) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Liu et al.)

A new 14-membered ring brominated macrolide glycoside, named moorenaside ( 1 ), was discovered from a marine cyanobacterial sample collected from Shands Key in Florida. The structure of 1 was established by analysis of spectroscopic data including its relative configuration. The absolute configuration was inferred from optical rotation data and comparison with related compounds. The structure of 1 features an α,β-unsaturated carbonyl system, which is also found in aurisides. The presence of this motif in 1 prompted us to evaluate its effect on Keap1/Nrf2 signaling, a cytoprotective pathway culminating in the activation of antioxidant genes activated upstream by the cysteine alkylation of Keap1. Moorenaside exhibited moderate ARE luciferase activity at 32 μM. Due to the established crosstalk between Nrf2 and NF-κB pathways, we investigated the anti-inflammatory effects of 1 in LPS-induced mouse macrophages (RAW264.7 cells), a commonly used model for inflammation. Moorenaside significantly upregulated Nqo1 (Nrf2 target gene) and downregulated iNos (NF-κB target gene) at 32 μM by 5.0- and 2.5-fold, respectively, resulting in a significant reduction of nitric oxide (NO) levels. Furthermore, we performed RNA-sequencing and demonstrated the transcriptional activity of 1 on a global level and identified canonical pathways and upstream regulators involved in inflammation, immune response, and certain oxidative-stress-underlying diseases such as multiple sclerosis and chronic kidney disease.

Acute lung injury (ALI) arises from an excessive inflammatory response, usually progressing to acute respiratory distress syndrome (ARDS) if not promptly addressed. There is currently a limited array of effective treatments available for ALI. In this study, we developed disulfide bond-bridged prodrug self-assembled nanoparticles (referred to as DSSS NPs). These nanoparticles were consisted of Dexamethasone (Dex) and stearic acid (SA), and were designed to target and treat ALI. DSSS NPs demonstrated a substantial drug loading capacity with 37.75 % of Dex, which is much higher than conventional nanomedicines (usually < 10 %). Moreover, they exhibited the potential to specifically target injured lung tissue and inflammatory microenvironment-responsive release drugs. Consequently, DSSS NPs reduced significantly the levels of pro-inflammatory cytokines and tissue damage in mice with ALI induced by lipopolysaccharide (LPS). Overall, DSSS NPs offer a promising strategy for treatment of acute lung injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Urtica dioica L. is one of the most widely utilized medicinal plants commonly applied in the form of tea, juice, and dietary supplements. This study aimed to assess the effect of the U. dioica ethanol-water extract (UdE) and polyphenolic fraction isolated from the extract (UdF) on normal human colon epithelial cells and to evaluate their protective activity against induced oxidative stress. The cytotoxic potential against human colorectal adenocarcinoma (HT29) and the anti-inflammatory effects were also investigated. UPLC-MS-DAD analysis revealed that both extracts were abundant in caffeic acid derivatives, specifically chlorogenic and caffeoylmalic acids, and therefore, they showed significant protective and ROS scavenging effects in normal human colon epithelial cells. Moreover, they had no negative impact on cell viability and morphology in normal cells and the extracts, particularly UdF, moderately suppressed adenocarcinoma cells. Furthermore, UdF significantly decreased IL-1β levels in HT29 cells. Our research indicates that U. dioica may provide significant health advantages because of its antioxidant and anti-inflammatory effects., Competing Interests: The authors declare no conflicts of interest.

Propolis, such as is used as bio-cosmetics and in functional materials, is increasing because of its antioxidant medicinal benefits. However, its pharmacological and chemical composition is highly variable, relative to its geography and botanical origins. Comparative studies on three propolis samples collected from different regions in Korea have been essential for linking its provenance, chemical composition, and biological activity, thereby ensuring the efficient utilization of its beneficial properties. Here, we report the chemical composition and biological activities such as the antioxidant, wound healing, and anti-inflammatory effects of the ethanolic extract of Korean propolis collected from two regions. We compared the chemical constituents of three 70% ethanol-extracted (EE) samples, including the Andong, Gongju field (GF), and Gongju mountain (GM)-sourced propolis using Gas chromatography-mass spectrometry (GC-MS). The major and common components of these EE Korean propolis were flavonoids such as pinocembrin (12.0-17.7%), chrysin (5.2-6.8%), and apigenin (5.30-5.84%). The antioxidant property using a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay of EEP showed substantial differences among samples with the highest from Andong. The sample 10% GM levigated in simple ointment was found to be the most active in wound healing activity based on the excision, incision, and dead space wound models. The potential of propolis for wound healing is mainly due to its evidenced properties, such as its antimicrobial, anti-inflammatory, analgesic, and angiogenesis promoter effects, which need further study. The anti-inflammatory activity and NO production inhibitory effect were highest in GM samples. However, GM and GF samples demonstrated similar inhibitory effects on the expression of inflammatory mediators such as iNOS, IL-1β, and IL-6. The presence of a higher concentration of flavonoids in Korean EE propolis might be responsible for their promising wound healing, anti-inflammatory, and antioxidant properties.