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The biosynthesis of nanomaterials is a vast and expanding field of study due to their applications in a variety of fields, particularly the pharmaceutical and biomedical fields. Various synthetic routes, including physical and chemical methods, have been developed in order to generate metal nanoparticles (NPs) with definite shapes and sizes. In this review, focused on the recent advancements in the green synthetic methods for the generation of silver, zinc and copper NPs with simple and eco-friendly approaches and the potential of the biosynthesized metal and metal oxide NPs as alternative and therapeutic agent for the treatment of inflammatory diseases. Inflammation is a body's own defense mechanism that can become chronic inflammation affecting healthy cells. Owning to the size-based advantages of NPs which can mitigate in theses medical conditions and serve as anti-inflammatory drugs. The factors influencing their physicochemical properties, toxicity, biocompatibility and mode of action to formulate an effective nanomedicine in the treatment of inflammation., 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 inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from inflammatory microenvironments. Macrophages infiltrate and polarize toward a pro-inflammatory phenotype (M 1 -like), thereby increasing the severity of inflammation. Therefore, we aimed to suppress the pro-inflammatory activity of M 1 -like macrophages and decrease their infiltration at the site of inflammatory insult to resolve tissue inflammation. To achieve this, we developed a theranostic curcumin-loaded nanoemulsion platform that delivers a low dose of curcumin, a known anti-inflammatory phytochemical, to macrophages and allows in vivo tracking of macrophages by near-infrared fluorescence (NIRF) imaging technique. In vitro, we showed that curcumin-loaded nanoemulsion suppressed polarization of macrophages towards M 1 -like phenotype, consequently decreasing the release of pro-inflammatory cytokines and mediators like IL-6, IL-[Formula: see text] TNF-[Formula: see text], and nitric oxide (NO). Furthermore, curcumin-loaded nanoemulsion increased the level of IL-10, an anti-inflammatory cytokine, and protected macrophages against ferroptosis compared to drug-free nanoemulsion. In a rodent model of Complete Freund's adjuvant (CFA)-induced inflammation, we demonstrated that infiltrating macrophages sequestered curcumin-loaded nanoemulsion droplets and acted as cellular drug depots at the site of inflammation. This consequently decreased macrophage infiltration at the CFA-induced inflammation site in both sexes compared to drug-free nanoemulsion, as demonstrated by NIRF imaging, H&E staining, and immunofluorescence. Taken together, our results indicated that the anti-inflammatory efficacy of curcumin was significantly improved when directly delivered to pro-inflammatory macrophages via theranostic nanoemulsion. This work opens an avenue for exploring theranostic nanoemulsions as a platform for delivering natural anti-inflammatory products for immune modulation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ursolic acid (3-hydroxy-urs-12-ene-28-oic acid, UA) is a pentacyclic triterpene present in numerous plants, fruits and herbs and exhibits various pharmacological effects. However, UA has limited clinical applicability since it is classified as BCS class IV molecule, characterized by low solubility, low oral bioavailability and low permeability. In the present study, UA was isolated from the biomass marc of Lavandula angustifolia and was structurally modified by an induction of indole ring at the C-3 position and amide group at the C-17 position with the aim to enhance its pharmacological potential. This modification resulted in the synthesis of a series of compounds which were investigated for their anti-inflammatory potential both in-vitro and in animal models in comparison to UA. In RAW 264.7 cells, UA and its derivatives were non-cytotoxic up to 10 µM. The derivative UA-1 exhibited a significantly lower IC 50 (2.2 ± 0.4 µM) for NO inhibition compared to UA (17.5 ± 2.0 µM). Molecular docking showed strong interactions of UA-1 with TNF-α and NF-κB. UA-1 significantly reduced LPS-induced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in RAW 264.7 macrophages with the inhibition levels of 74.2 ± 2.1 % for TNF-α, 55.9 ± 3.7 % for IL-6 and 59.7 ± 4.2 % for IL-1β at 5.0 µM, respectively and reactive oxygen species while upregulating anti-inflammatory cytokine, IL-10. It also downregulated iNOS, COX-2, p-NF-κB p65, and p-IκBα at both mRNA and protein levels. In LPS-induced systemic inflammation mice model, UA-1 significantly lowered NO, TNF-α, IL-6, IL-1β and serum biochemical parameters, reduced tissue damage, and exhibited improved aqueous solubility and moderate lipophilicity. Overall, UA-1 demonstrated superior anti-inflammatory potential, improved solubility, and better therapeutic potential compared to UA., 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 Inc. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by synovial hyperplasia, where inflammatory macrophages within the joint synovium produce multiple inflammatory cytokines, leading to cartilage damage. The development of therapeutic strategies that combine anti-inflammatory effects and cartilage repair mechanisms holds great promise for effective RA treatment. To address the limitations associated with the off-target effects of intravenous administration and the risk of synovial cavity infection with repeated local injections, we have innovatively developed a liposomal drug depot through hyaluronic acid (HA)-modified liposomes encapsulating dexamethasone sodium phosphate (DSP)-loaded nanogels, termed HA-Lipo@G/D. The nanogels were prepared by ionic cross-linking of chondroitin sulfate and gelatin, both of which have notable cartilage repair properties. In vitro studies demonstrated that this formulation exhibited sustained drug release, enhanced uptake by inflammatory macrophages, reduced secretion of inflammatory factors (TNF-α, IL-1β), and significantly decreased chondrocyte apoptosis induced by inflammatory factors. Moreover, in vivo assessments in a rat model of collagen-induced arthritis revealed effective accumulation of the liposomal drug depot at the inflamed joint site, resulting in macrophage repolarization and cartilage tissue repair. Our findings provide a synergistic strategy for inhibiting inflammation and mitigating cartilage damage through local joint cavity injection, thereby enhancing the therapeutic efficacy of RA., Competing Interests: Declarations. Ethics approval and consent to participate: Relevant studies were carried out with the approval of the Ethics Committee of the Southwest Medical University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Osteoarthritis (OA) has long been considered a disease of the articular cartilage. Within the past decade it has become increasingly clear that OA is a disease of the entire joint space and that interactions between articular cartilage and subchondral bone likely play an important role in the disease. Driven by this knowledge, we have created a novel microphysiological model of the osteochondral unit containing synovium, cartilage, bone, and vasculature in separate compartments with molecular and direct cell-cell interaction between the cells from the different tissue types. We have characterized the model in terms of differentiation by molecule and matrix secretion and shown that it demonstrates morphology and functionality that mimic the native characteristic of the joint space. Finally, we induced inflammation and subsequently rescued the model constructs by a known compound as proof of concept for anti-inflammatory drug screening applications.

Atherosclerosis (AS) is a prevalent inflammatory vascular disease characterized by plaque formation, primarily composed of foam cells laden with lipids. Despite lipid-lowering therapies, effective plaque clearance remains challenging due to the overexpression of the CD47 molecule on apoptotic foam cells, inhibiting macrophage-mediated cellular efferocytosis and plaque resolution. Moreover, AS lesions are often associated with severe inflammation and oxidative stress, exacerbating disease progression. Herein, we introduce a multifunctional nanomedicine (CEZP) targeting AS pathogenesis via a "cell efferocytosis-lipid degradation-cholesterol efflux" paradigm, with additional anti-inflammatory properties. CEZP comprises poly(lactic- co -glycolic acid) nanoparticles encapsulated within a metal-organic framework shell coordinated with zinc ions (Zn 2+ ) and epigallocatechin gallate (EGCG), enabling CpG encapsulation. Upon intravenous administration, CEZP accumulates at AS plaque sites, facilitating macrophage uptake and orchestrating AS treatment through synergistic mechanisms. CpG enhances cellular efferocytosis, Zn 2+ promotes intracellular lipid degradation, and EGCG upregulates adenosine 5'-triphosphate-binding cassette transporters for cholesterol efflux while also exhibiting antioxidant and anti-inflammatory effects. In vivo validation confirms CEZP's ability to stabilize plaques, reduce lipid burden, and modulate the macrophage phenotype. Moreover, CEZP is excreted from the body without safety concerns, offering a low-toxicity nonsurgical strategy for AS plaque eradication.

Astaxanthin is a red-orange keto-carotenoid exhibiting antioxidant activity. AST is mainly used in the cosmetic, food, and healthcare industries. Nevertheless, because of its anti-inflammatory effects and immune modulation activity, AST use in pharmacology has been proposed as an alternative for treating neurodegenerative disorders, inflammatory bowel disease, arthritis, atherosclerosis, or diabetic foot ulcers, among others. However, before an AST clinical implementation, it is still necessary to solve challenges related to the use of AST, such as lack of solubility, poor bioavailability, and sensitivity to light, oxygen, and temperature. For that reason, the development of several biomaterials to encapsulate, protect, and dosage AST has been proposed in recent years. This review discusses the use of liposomes, hydrogels, and polymer micro and nanoparticles as vehicles for AST release based on available literature. Additionally, an analysis of released, encapsulated, and effective AST doses is presented, as well as the regulatory landscape of different delivery systems to reveal details of AST delivery, which should inform future strategies for implementing AST in the clinic., 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.)

Interleukin-1 receptor-associated kinase 4 (IRAK4) is involved in various inflammation-related diseases. Both the kinase and scaffolding functions of IRAK4 initiate pro-inflammatory factor transcription and expression. The scaffolding function of IRAK4 is essential for Myddosome assembly and NF-κB activation. Conventional small-molecule inhibitors effectively inhibit the kinase function of IRAK4 but do not block its scaffolding function. Recently, various IRAK4 degraders have shown promising therapeutic potential in inflammatory diseases. The most advanced IRAK4-selective degrader, KT-474 (SAR444656), significantly reduced inflammatory biomarker levels in patients and demonstrated high safety and tolerability. This perspective introduces and discusses the physiological biology of IRAK4, its associated diseases, and the current development of IRAK4 degraders, thereby offering insights into future research directions.

Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease characterized by the presence of numerous proinflammatory cytokines, massive reactive oxygen species (ROS) and excess lipids, which together result in an overall inflammatory positive feedback loop in the plaque focus. Due to its excellent enzyme-like activity in ROS scavenging and inflammation inhibition, as well as its photothermal effects in the lipid efflux ability of foam cells, Prussian blue (PB) has greater potential in preventing inflammatory factor loops for enhanced treatment of AS than traditional nanozymes. In this study, the multifunctional nanozyme BSA@PB/Cur was synthesized by self-assembly of bovine serum albumin (BSA) with PB and further encapsulation of the anti-inflammatory drug curcumin (Cur). The in vitro results showed that BSA@PB/Cur could effectively scavenge ROS and inhibit the expression of the inflammatory cytokines TNF-α and IL-1β as well as enhance the expression of ABCA1 and ABCG1 in foam cells, promote cholesterol efflux and inhibit foam cell formation. The in vivo experimental results demonstrated that BSA@PB/Cur could target plaque locations, significantly efflux the lipid content, and decrease the matrix metalloproteinase expression. This research provides a potential strategy for alleviating the persistent inflammatory feedback loop within the plaque microenvironment for AS treatment.

Significant progress has been made in the development of potential therapies for diseases associated with inflammation and oxidative stress. Nevertheless, the availability of effective clinical treatments remains limited. Herein, we introduce a novel silk-based bioactive material, TPSF, developed by sequentially conjugating Tempol and phenylboronic acid pinacol ester to silk fibroin. This innovative reactive oxygen species (ROS) scavenging material not only effectively eliminates free radicals and hydrogen peroxide but also readily self-assembles into nanoparticle forms (TPSN). In vitro experiments have demonstrated that TPSN exhibits significant anti-inflammatory activities and cytoprotective effects against ROS-mediated damage. Consistently, in murine models of acute lung and kidney injury, TPSN outperforms the small-molecule antioxidant NAC, exhibiting superior therapeutic efficacy. Mechanistically, TPSN has the capability to reprogram M1-like macrophages toward an M2-like state. Importantly, biocompatibility assays confirm that TPSN has good safety profiles. Consequently, TPSN, characterized by its favorable protective effects and excellent biocompatibility, exhibits considerable promise as a therapeutic intervention for inflammation-related diseases. This innovative strategy, which incorporates multifunctional antioxidant components into the silk fibroin matrix, effectively addresses oxidative stress and acute inflammation. Furthermore, it highlights the potential of modified silk fibroin materials in the management and mitigation of inflammation-led tissue damage., Competing Interests: Declarations. Ethical approval: All animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals recommended by the National Institutes of Health. All procedures and protocols were approved by the Animal Ethics Committee at Third Military Medical University (Chongqing, China), approval No. AMUWEC20230257. Consent for publication: All authors agree for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The development of inflammation has an indispensable importance in the self-protection of the human body. However, over-inflammation may damage human health, and inflammatory pathways and inflammasomes have a significant impact on the onset of inflammation. Therefore, how to constrain the development of inflammation through inflammatory pathways or inflammasomes becomes a hot research issue. Carotenoids are a natural pigment and an active substance in algae, with anti-inflammatory and antioxidant effects. Many studies have shown that carotenoids have inhibitory effects on the inflammatory pathways and inflammasomes. In this review, we discussed the mechanism of carotenoids targeting those important inflammatory pathways and their effects on common inflammasome NLRP3 and inflammation-related diseases from the perspective of several inflammatory pathways, including p38 MAPK, IL-6/JAK/STAT3, and PI3K, with a focus on the targets and targeting effects of carotenoids on different inflammatory signaling pathways, and at last proposed possible anti-inflammatory targets., Competing Interests: Declaration of competing interest The author 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 Masson SAS. All rights reserved.)

The applications of nanomaterials in regenerative medicine encompass a broad spectrum. The functional nanomaterials, such as Prussian blue and its derivative nanoparticles, exhibit potent anti-inflammatory and antioxidant properties. By combining it with the corresponding scaffold carrier, the fusion of nanomaterials and biotherapy can be achieved, thereby providing a potential avenue for clinical treatment. The present study demonstrates the fabrication of a Mesoporous Prussian blue nanoparticles (MPBN) functionalized Inverse Opal Film (IOF) neuroconduit for peripheral nerve repair through reverse replication and freeze-drying techniques. The binding of MPBN to the neuroconduit can effectively decreasing reactive oxygen species and inflammatory factors in the vicinity of the residual nerve, thereby providing protective effects on the damaged nerve. Furthermore, comprehensive behavioral, electrophysiological, and pathological analyses unequivocally substantiate the efficacy of MPBN in increasing nerve structure regeneration and ameliorating denervation-induced myopathy. Moreover, MPBN enhances the antioxidant capacity of Schwann cells by activating the AMPK/SIRT1/PGC-1 pathway. The findings suggest that MPBN, a biocompatible nanoparticle, can safeguard damaged nerves by optimizing the microenvironment surrounding nerve cells and augmenting the antioxidant capacity of nerve cells, thereby facilitating nerve regeneration and repair. This also establishes a theoretical foundation for exploring the integration and clinical translation between nanomaterials and biotherapy., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures and animal experiments were performed in compliance with the Animal Care and Use Committee of Wenzhou Medical University. All contributing authors agree to the publication of this article. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Non-invasive imaging techniques employing biomarkers with high selectivity for inflammation are essential not only for the early diagnosis and prevention of chronic inflammatory diseases but also for guiding appropriate drug therapy and enabling real-time evaluation of anti-inflammatory drug efficacy. In this study, we conjugated radioactive zirconium to sorbitol, a compound that can selectively target inflammation, and evaluated its inflammation-specific uptake and potential for assessing anti-inflammatory treatment efficacy in a mouse inflammation model. Pharmacokinetic analysis demonstrated that radiolabeled sorbitol achieved maximal uptake in inflamed tissues within 1 h. Positron emission tomography imaging further confirmed its utility in monitoring therapeutic effects during anti-inflammatory drug treatment. Our findings suggest that [ 89 Zr]DTPA-sorbitol is a promising radioprobe for targeting rapid systemic inflammation, particularly in tissues demonstrating minimal non-specific uptake, such as the brain, heart, and lung tissues. Additionally, it holds significant potential for the in vivo evaluation of anti-inflammatory drug efficacy.

Inflammation is a vital and normal physiological response; however, excessive inflammation can contribute to the development of various diseases. Artemisia sieversiana, a traditional Chinese medicinal plant, contains a variety of chemical compounds. One such compound, 3-oxo-11αH-germacra-1(10)E,4Z-dien-12,6α-olide, a germacranolide sesquiterpenoid (germacranolide, GMO), has not been thoroughly investigated regarding its potential anti-inflammatory properties. In this study, the anti-inflammatory and antioxidant properties of GMO were investigated for the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. It was demonstrated that GMO effectively suppressed the production of inflammatory mediators, decreased the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) in RAW264.7 cells. Additionally, GMO exhibited the capacity to mitigate oxidative damage induced by LPS, as indicated by assessments of reactive oxygen species and mitochondrial membrane potential. In summary, GMO possesses significant anti-inflammatory effects by modulating the NF-κB/MAPK pathway and antioxidant effects by regulating ROS production., Competing Interests: Declarations. Conflict of interest: The authors declare that there is no conflict of interest., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

This study aimed to elucidate the mechanism that total alkaloids in Anisodus tanguticus (AT)(Maxim.) Pascher played anti-inflammatory and analgesic effects. In this paper, the anti-inflammatory effect in the total alkaloids of AT was confirmed via lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 cells and the main components of AT were immediately analyzed by UPLC/MS. Disease targets were obtained in GeneCards and DisGeNET. Targets of major compounds were searched in ETCM, TCMSP and other databases. The protein-protein interaction (PPI) network was constructed using STRING database, and Cytoscape was used for core targets screening. GO and KEGG enrichment analysis were performed using Daivid database. Sailvina was used for molecular docking. Molecular dynamics simulation analysis was performed using the Amber 20 program. The results showed that the main components in AT were anisodamine, atropine, fabiatrin, scopolamine, scopoletin and scopolin, possibly exerting anti-inflammatory and analgesic effects through pathways such as EGFR tyrosine kinase inhibitor resistance and IL-17 signaling pathway. Fabiatrin and scopolin could be potential drugs with good anti-inflammatory and analgesic effects., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Chronic inflammation is a common characteristic of all kinds of diseases, including autoimmune diseases, metabolic diseases, and tumors. It is distinguished by the presence of low concentrations of inflammatory factors stimulating the body for an extended period, resulting in a persistent state of infection. This condition is manifested by the aggregation and infiltration of mononuclear cells, lymphocytes, and other immune cells, leading to tissue hyperplasia and lesions. Although various anti-inflammatory medications, including glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), have shown strong therapeutic effects, they lack specificity and targeting ability, and require high dosages, which can lead to severe adverse reactions. Nanoparticle drug delivery mechanisms possess the capacity to minimize the effect on healthy cells or tissues due to their targeting capabilities and sustained drug release properties. However, most nanosystems can only target the inflammatory sites rather than specific types of immune cells, leaving room for further improvement in the therapeutic effects of nanomaterials. This article reviews the current research progress on the role of diverse immune cells in inflammation, focusing on the functions of neutrophils and macrophages during inflammation. It provides an overview of the domestic and international applications of nanomaterials in targeted therapy for inflammation, aiming to establish a conceptual foundation for the utilization of nanomaterials targeting immune cells in the treatment of chronic inflammation and offer new perspectives for the avoidance and management of inflammation., Competing Interests: All authors declared no conflicts of interest in this work., (© 2024 Ci et al.)

Background: The multi-biological barriers present in the inflammatory microenvironment severely limit the targeted aggregation of anti-inflammatory drugs in the lesion area. However, conventional responsive drug carriers inevitably come into contact with several pro-responsive stimulatory mediators simultaneously, leading to premature drug release and loss of most therapeutic effects. Breaking through the multi-level barriers of the inflammatory microenvironment is essential to improve the enrichment and bioavailability of drugs., Results: In this study, we propose a novel two-stage structural strategy to build shielded cascades of targeted nanocarriers (FA-PTP@Que) through inflammatory mediators, using cascade structures to cross multiple environmental barriers. The cascade structure of FA-PTP@Que is responsive to inflammatory mediators and exhibits ideal pathological microenvironmental response and drug release properties. FA-PTP@Que has shown good macrophage regulation and anti-inflammatory effects by efficiently targeting macrophages, scavenging intracellular reactive oxygen species (ROS), and down-regulating the secretion of pro-inflammatory factors. Significantly, in mice with arthritis and colitis, FA-PTP@Que enriches and targets macrophages at the sites of arthritis and colitis, showing significant anti-inflammatory effects., Conclusion: FA-PTP@Que combines active chemotaxis of nanocarriers to inflammatory tissues and active targeting of effector cells, acting precisely at each barrier level in different microenvironments by responding to inflammatory mediators and overcoming the multiple barriers in the inflammatory microenvironment. This innovative strategy can effectively break through various inflammatory microenvironments and has the potential application to other inflammatory diseases., Competing Interests: Declarations. Ethics approval and consent to participate: The animal handling and surgical procedures were conducted by the protocols approved by the Ethics Committee of the Affiliated Stomatological Hospital of Chongqing Medical University (2022(No. 064)). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The p38 mitogen-activated protein kinase (MAPK) pathway is pivotal in regulating inflammatory responses and has emerged as a key target for the development of small-molecule inhibitors aimed at treating inflammatory diseases. In arthritis, especially rheumatoid arthritis (RA), the p38 MAPK pathway contributes to chronic inflammation and joint destruction by promoting the production of pro-inflammatory cytokines. Preclinical studies have shown that small-molecule inhibitors targeting the p38 MAPK pathway hold significant promise, exhibiting the potential to reduce inflammation and preserve joint integrity. Targeting this pathway presents a novel therapeutic approach to mitigating inflammation. This review traces the evolution of p38 MAP kinase inhibitors from initial laboratory studies to clinical candidates, underscoring their potential to significantly alter the treatment approach for 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 Elsevier Masson SAS. All rights reserved.)

Histone deacetylases (HDACs) are enzymes that play an essential role in the onset and progression of cancer. As a consequence, a variety of HDAC inhibitors (HDACis) have been developed as potent anticancer agents, several of which have been approved by the FDA for cancer treatment. However, recent accumulated research results have suggested that HDACs are also involved in several other pathophysiological conditions, such as fibrotic, inflammatory, neurodegenerative, and autoimmune diseases. Very recently, the HDAC inhibitor givinostat has been approved by the FDA for an indication beyond cancer: the treatment of Duchenne muscular dystrophy. In recent years, more and more HDACis have been developed as tools to understand the role that HDACs play in various disorders and as a novel therapeutic approach to fight various diseases other than cancer. In the present perspective article, we discuss the development and study of HDACis as anti-fibrotic and anti-inflammatory agents, covering the period from 2020-2024. We envision that the discovery of selective inhibitors targeting specific HDAC isozymes will allow the elucidation of the role of HDACs in various pathological processes and will lead to the development of promising treatments for such diseases.

Microsomal prostaglandin E 2 synthase 1 (mPGES-1) is a promising target for treating inflammatory diseases and pain. This study introduces a novel series of benzimidazoles, with the most potent analogs exhibiting IC 50 values of 0.27-7.0 nM in a cell-free assay for prostaglandin (PG)E 2 production. Compound 44 (AGU654) demonstrated remarkable selectivity for mPGES-1 (IC 50 = 2.9 nM) over COX-1, COX-2, 5-LOX, and FLAP, along with excellent bioavailability. Metabololipidomics analysis with activated human monocyte-derived macrophages and human whole blood revealed that AGU654 selectively suppresses PGE 2 production triggered by bacterial exotoxins while sparing other prostaglandins. Furthermore, in vivo studies showed that AGU654 significantly alleviated fever, inflammation, and inflammatory pain in preclinical guinea pig models, suggesting that it could be an effective strategy for managing inflammatory diseases. In conclusion, these benzimidazole derivatives warrant further exploration into new and alternative analogs, potentially uncovering novel compounds with a favorable pharmacological profile possessing significant anti-inflammatory and analgesic properties.

As a defense mechanism against deleterious stimuli, inflammation plays a vital role in the development of many disorders, including atherosclerosis, inflammatory bowel disease, experimental autoimmune encephalomyelitis, septic and non-septic shock, and non-alcoholic fatty liver disease (NAFLD). Despite the serious adverse effects of extended usage, traditional anti-inflammatory medications, such as steroidal and non-steroidal anti-inflammatory medicines (NSAIDs), are commonly used for alleviating symptoms of inflammation. The PPARδ subtype of peroxisome proliferator-activated receptors (PPARs) has attracted interest because of its potential for reducing inflammation and related disorders. In this study, a series of 1,3,4-thiadiazole derivatives were designed, synthesized, and evaluated. Compound 11 exhibited potent PPARδ agonistic activity with EC 50 values 20 nM and strong selectivity over PPARα and PPARγ. Furthermore, compound 11 demonstrated favorable in vitro and in vivo pharmacokinetic properties. In vivo experiments using labeled macrophages and paw thickness measurements confirmed compound 11's potential to reduce macrophage infiltration and alleviate inflammation. These findings highlight compound 11 as a potent and promising therapeutic candidate for the treatment of acute inflammatory diseases and warrant further investigation to explore various biological roles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jungwook chin reports financial support was provided by National Research Foundation of Korea. Taeho Lee reports financial support was provided by National Research Foundation of Korea. Jungwook chin has patent #PCT/KR2023/003210 pending to Daegu-Gyeongbuk Medical Innovation Foundation. If there are other authors, they 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 Masson SAS. All rights reserved.)

Myricetin (MYR) is a natural flavonoid that has several biological functions. However, some of its beneficial effects are diminished due to low water solubility, stability, and bioavailability. Herein, several kinds of silica nanoparticles (MCM-41 and SBA-15) were loaded with MYR to improve its biological activity as an analgesic, antipyretic, and anti-inflammatory component, thereby overcoming its drawbacks. The nanoparticles (MYR@SBA-15) were formulated optimally, transforming MYR into an amorphous state. This transformation was confirmed via several strategies, including differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder x-ray diffraction. As a result, there was a significant enhancement in the solubility and rate of dissolution in water. The anti-inflammatory benefits as an innovative strategy and the underlying mechanism of action of MYR and its SBA-15 silica nanoparticles (MYR@SBA-15) were investigated based on the biochemical, histological, immunohistochemical, and metabolomic assays alongside their antipyretic and analgesic characteristics. Compared to the usage of raw MYR, the administration of MYR@SBA-15 at doses of 25, 50, and 100 mg/kg significantly decreases pain perception by inhibiting the body's writhing motions induced by acetic acid. Furthermore, it helps regulate increased body temperature caused by baking yeast and effectively stabilizes it. It reduces the release of NO and PGE-2 in a concentration-dependent manner by down-regulating iNOS and COX-2 expression in the inflammatory model. MYR and MYR@SBA-15 also inhibit the nuclear translocation of NF-κB, downregulate the expression of mitogen-activated protein kinases (MAPKs), such as p38, ERK1/2, and JNK protein, and reduce the generation of proinflammatory cytokines, such as TNF-α. In addition, inflammatory cardinal signs like paw edema caused by carrageenan in rats are greatly suppressed by MYR and MYR@SBA-15 treatment when compared to the untreated group. More noteworthy outcomes are shown in the MYR@SBA-15, particularly at a dose of 100 mg/kg. These results of biochemical and immuno-histochemistry suggest that MYR@SBA-15 may be a useful analgesic antipyretic and may also help reduce inflammation by altering MAPKs/NF-κB and COX-2/PGE-2 signaling cascades. Serum metabolomics study demonstrated modifications in various low molecular weight metabolites with arthritis development. These metabolite levels were restored to normal when MYR@SBA-15 was administered via modulating several metabolic pathways, i.e., pyrimidine, energy metabolism, and proteins. Overall, MYR-loaded SBA-15 silica nanoparticles have demonstrated significant promise in enhancing the disturbed metaboloic pathways and providing a substantial capacity to regulate several oxidative stress and inflammatory mediators., 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 is central to numerous diseases, highlighting the need for new anti-inflammatory agents. This study explores the potential of novel spirofused indoline-quinazoline hybrids (4a-p) as anti-inflammatory compounds, inspired by a spiroisatin analogue (VI) that showed modest TNF-α inhibition. We aimed to enhance activity by modifying the isatin scaffold: first, introducing N-alkylation (propyl, butyl, or isobutyl) to improve hydrophobic interactions within the TNF-α dimer active site; second, adding halogens (F, Cl, Br) at the 5-position to increase lipophilicity. Anti-inflammatory activity against TNF-α was confirmed in-vivo for all synthesized analogues, with 4b, 4e, 4k, and 4n emerging as the top candidates. Further studies on these four compounds assessed their analgesic effects, as well as their impact on PGE 2 , NF-κB, paw thickness, and paw weight. In-vitro analyses revealed nanomolar TNFR2-TNF-α binding inhibition for the four leads. Safety evaluations included histopathology, ulcerogenic potential, kidney and liver functions, and acute hemotoxicity. In-silico studies examined drug-likeness, pharmacokinetics, and TNF-α dimer interactions. These results suggest that the four lead compounds possess promising profiles compared to standard therapies., Competing Interests: Declaration of competing interest There are no interests to declare. The author declared no potential 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 is a physiological response of the body to harmful stimuli such as pathogens, damaged cells, or irritants, involving a series of cellular and molecular events. It is associated with various diseases including neurodegenerative disorders, cancer, and atherosclerosis, and is a leading cause of global mortality. Key inflammatory factors, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), RANTES (CCL5), and prostaglandins, play central roles in inflammation and disease progression. Traditional treatments such as NSAIDs, steroids, biologic agents, and antioxidants have limitations. Recent advancements in nanomaterials present promising solutions for treating inflammation-related diseases. Unlike nanomaterials that rely on passive targeting and face challenges in precise drug delivery, nanomotors, driven by chemical or optical stimuli, offer a more dynamic approach by actively navigating to inflammation sites, thereby enhancing drug delivery efficiency and therapeutic outcomes. Nanomotors allow for controlled drug release in response to specific environmental changes, such as pH and inflammatory factors, ensuring effective drug concentrations at disease sites. This active targeting capability enables the use of smaller drug doses, which reduces overall drug usage, costs, and potential side effects compared to traditional treatments. By improving precision and efficiency, nanomotors address the limitations of conventional therapies and represent a significant advancement in the treatment of inflammation-related diseases. This review summarizes the latest research on nanomotor-mediated treatment of inflammation-related diseases and discusses the challenges and future directions for optimizing their clinical translation., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Acute lung injury (ALI) remains a devastating clinical condition with limited therapeutic options. While Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2) has emerged as a critical mediator in ALI pathogenesis, effective SHP2-targeting therapeutics remain largely elusive. Baliospermum solanifolium (Burm.) is a traditional medicine used to treat various diseases such as asthma, edema, bronchitis, jaundice, and constipation. Baliosperoid A (BA), a diterpenoid compound derived from Baliospermum solanifolium's roots, exhibits potent NO inhibitory activity in RAW264.7 cells. However, its anti-inflammatory activity and potential targets have never been reported. Here, we report BA acts as a selective SHP2 inhibitor with remarkable therapeutic potential against ALI. Through comprehensive molecular and functional analyses, we demonstrate that BA directly binds to and inhibits SHP2 phosphatase activity with high specificity (IC 50  = 1.638 ± 0.324 μM). Mechanistically, BA orchestrates a dual-action therapeutic effect by simultaneously suppressing inflammatory cascades through SHP2-mediated MAPK and NF-κB pathway inhibition while activating the Nrf2-dependent antioxidant response. In preclinical models of ALI and sepsis, BA treatment significantly improved survival rates, preserved lung architecture, and prevented multi-organ dysfunction. Notably, BA demonstrated superior efficacy to the existing SHP2 inhibitor SHP099, particularly in sepsis survival outcomes (90 % vs 50 % survival at 24 h). Our findings not only identify BA as a promising therapeutic candidate for ALI but also establish a novel paradigm for targeting SHP2 in 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 Elsevier Inc. All rights reserved.)

Background: An increasing incidence of metabolic disorders emphasizes the need to explore natural treatments. Spirulina, a microalga with a rich nutrient profile, offers a promising solution for obesity, diabetes, and inflammation. This study provides a meticulous analysis of spirulina powder, evaluating its physicochemical attributes and technofunctional properties through the use of advanced analytical techniques., Results: Spirulina powder demonstrated strong flowability, substantial water and oil absorption capacity, and moderate foaming characteristics. The ethanolic extract of spirulina was found to be a repository of phenolic (6.93 mg GAE/g) and flavonoid (7.17 mg QE/g) compounds, manifesting considerable antioxidant activity with a 58.49 g kg -1 inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. The extract also exhibited pronounced inhibitory effects on lipase and amylase enzymes, with inhibition percentages of 72.05 g kg -1 and 70.28 g kg -1 , respectively, and displayed a glucose retention capacity of 1.28 mg dL -1 (68.52 g kg -1 ) in a dialysis membrane assay. These results suggest its efficacy in modulating obesity and glycemic control. The powder also showed a potent anti-inflammatory response by mitigating protein denaturation., Conclusion: Spirulina powder is a potent natural agent with multiple health benefits, meriting its incorporation into functional foods. It could be suitable for application in the food industry, offering a natural strategy to combat metabolic diseases. This research adds to the scientific literature on spirulina, paving the way for future research into its utilization. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Portieria hornemannii , a marine red alga, has attracted considerable attention due to its possible therapeutic characteristics. NFκB, a crucial transcription factor involved in regulating immune and inflammatory responses, plays a central role in controlling the expression of various genes associated with inflammation, such as MMP 9. This study employed an aqueous extract of Portieria hornemannii (Ph) and subjected it to UV-Visible, FTIR spectroscopy, and GC-MS analysis to identify its phytochemical composition. The presence of Vanillin, tert-butyldimethylsilyl ether, Dodecane, 1-fluoro-, and Pentanoic acid, 5-hydroxy-2,4-di-t-butylphenyl esters in Ph indicates their potential anti-inflammatory properties, suggesting their potential application in inflammation treatment. In summary, Ph exhibited anti-inflammatory properties by modulating the expressions of NFκB-associated MMP 9 in zebrafish embryos, potentially reducing the risk of inflammatory diseases.

Fungi play a fundamental role in the marine environment, being promising producers of bioactive molecules in the pharmacological and industrial fields, which have demonstrated potential health benefits against cardiovascular and other chronic diseases. This review pertains to the analysis of the lipid compositions across various species of marine fungi and their constantly discovered substances, as well as their anti-inflammatory, antioxidant, and antithrombotic effects. The health-promoting aspects of these microorganisms will be explored, through the investigation of several mechanisms of action and interference of their bioactives in biochemical pathways. Despite exceptional results in this field, the potential of marine microorganisms remains largely unexplored due to the limited number of specialists in marine microbiology and mycology, a relatively recent science with significant contributions and potential in biodiversity and biotechnology., Competing Interests: The authors declare no conflicts of interest.

Haematococcus pluvialis contains valuable bioactive compounds, including astaxanthin, proteins, and fatty acids. Astaxanthin is known for its various health benefits, such as preserving the redox balance and reducing inflammation. However, its low stability and poor water solubility present challenges for various applications. Hot-melt extrusion (HME) technology enhances the aqueous solubility of H. pluvialis extracts, increasing the usable astaxanthin content through nanoencapsulation (HME-DDS-applied extracts, ASX-60F and ASX-100F). This study compared the effects of HME-DDS-derived extracts (ASX-60F and ASX-100F) and the non-applied extract (ASX-C) under inflammatory and oxidative stress conditions. In animal models of sepsis, 60F and 100F treatment exhibited higher survival rates and a lower expression of pro-inflammatory biomarkers compared to those treated with C. In lipopolysaccharide-stimulated RAW 264.7 macrophages, nitric oxide (NO) production and the expression of pro-inflammatory mediators such as cyclooxygenase-2 and inducible NO synthase were reduced by 60F or 100F treatments via ERK/p-38 mitogen-activated protein kinase (MAPK) signaling. Moreover, 60F or 100F inhibited reactive oxygen species production regulated by nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Collectively, these findings suggest that HME-DDS-derived H. pluvialis extracts exert anti-inflammatory and antioxidant effects by inhibiting MAPK phosphorylation and activating Nrf2/HO-1 expression.

Evidence has accumulated that Cannabis -derived compounds have the potential to treat neuroinflammatory changes present in neurodevelopmental conditions such as autism spectrum disorder. However, research is needed on the specific brain health benefits of strains of whole Cannabis extract that are ready for commercial production. Here, we explore the anti-inflammatory and neuroprotective effects of NTI-164, a genetically unique high-cannabidiol (CBD), low-Δ9-tetrahydrocannabinol extract, and also CBD alone on BV-2 microglia and SHSY-5Y neurons. Inflammation-induced up-regulation of microglial inflammatory markers was significantly attenuated by NTI-164, but not by CBD. NTI-164 promoted undifferentiated neuron proliferation and differentiated neuron survival under excitotoxic conditions. These effects suggest the potential for NTI-164 as a treatment for neuropathologies.

Moisture loss, infection, and severe inflammatory reactions are the primary factors affecting burn wound healing and leading to scar formation. Herein, we developed a quercetin-loaded polysaccharide-based injectable hydrogel (named PECE). The PECE consists of oxidized sodium alginate (OAlg) coupled with chitosan (CS) via Schiff bases and electrostatic interactions, while Que is incorporated via hydrogen bonding. Benefiting from the hydroxyl and carboxyl groups, PECE features distinguished moisturizing ability. Additionally, the sustained release of Que imparts remarkable antibacterial activity against Escherichia coli and Staphylococcus aureus . Likewise, PECE demonstrates favorable in vitro anti-inflammatory capacity as released Que significantly downregulates pro-inflammatory factors (IL-6 and TNF-α) secreted by RAW 264.7 macrophages. More importantly, in a rat model of deep second-degree burn wounds, PECE effectively inhibits wound infection, reduces inflammation, and promotes angiogenesis and collagen deposition, ultimately minimizing scar formation. Overall, this work presents a promising strategy for scarless healing of burn wounds.

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.)

New approaches to treat autoimmune diseases are needed, and we can be inspired by mechanisms in immune tolerance to guide the design of these approaches. Efferocytosis, the process of phagocyte-mediated apoptotic cell (AC) disposal, represents a potent tolerogenic mechanism that we could draw inspiration from to restore immune tolerance to specific autoantigens. ACs engage multiple avenues of the immune response to redirect aberrant immune responses. Two such avenues are: phosphatidylserine on the outer leaflet of the cell and engaging the aryl hydrocarbon receptor (AhR) pathway. We incorporated these two avenues into one acetalated dextran (Ace-DEX) microparticle (MP) for evaluation in vitro. First phosphatidylserine (PS) was incorporated into Ace-DEX MPs and evaluated for cellular association and mediators of cell tolerance including IL-10 production and M2 associated gene expression when particles were cultured with peritoneal macrophages (PMacs). Further PS Ace-DEX MPs were evaluated as an agent to suppress LPS stimulated PMacs. Then, AhR agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) was incorporated into Ace-DEX MPs and expression of M2 and IL-10 genes was evaluated in PMacs. Further the ITE and PS Ace-DEX MPs (PS/ITE MPs) were evaluated for suppression of T cell priming and Th1 polarization. Our results indicate that the PS/ITE-MPs stimulated anti-inflammatory cytokine expression and suppressed inflammation following LPS stimulation of PMacs. Moreover, PS/ITE MPs induced the anti-inflammatory enzyme IDO1 and suppressed macrophage-mediated T cell priming and Th1 polarization. These findings suggest that PS and ITE-loaded Ace-DEX MPs could be a promising therapeutic tool for suppressing inflammation., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) is a downstream protein from the pattern recognition receptor family that forms the NLRP3 inflammasome. The NLRP3 inflammasome releases caspase-1, IL-1β, and IL-18, contributing to inflammatory responses associated with diabetes mellitus, arthritis, and ischemia-reperfusion injury. Recent studies suggest that specific saponin monomers and extracts from traditional Chinese medicines can inhibit inflammatory responses and related pathways, including the production of inflammatory factors. MCC950 is one of the most influential and specific NLRP3 inhibitors. Comparative molecular docking studies have identified 22 of the 37 saponin components as more robust binders to NLRP3 than MCC950. Dioscin, polyphyllin H, and saikosaponin-a have the highest binding affinities and potential NLRP3 inhibitors, offering a theoretical basis for developing novel anti-inflammatory therapies., Competing Interests: Declarations. Conflicts of interest: The authors declare that they have no conflicts of interest., (© 2024. The Pharmaceutical Society of Korea.)

The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate ( EPPP ), and its 1:1 complex with β-cyclodextrin ( EPPPβCD ) have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of EPPPβCD in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of EPPPβCD on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4 + CD25 + fractions at the onset of inflammation. This effect is attributed to the inhibition of Treg proliferation, which is crucial in hastening the resolution of inflammation. These findings underscore the potential of EPPPβCD as a promising therapeutic agent in controlling and mitigating inflammation mediated by heavy metal exposure, thereby offering a new avenue for the development of anti-inflammatory treatments.

Cell-free DNA (cfDNA) scavenging represents a promising anti-inflammatory modality for autoimmune disease (AID) treatment. However, it remains challenging for existing systems to achieve inflammation-targeted cfDNA scavenging and the management of cfDNA-unrelated inflammatory pathways. Herein, inflammation-responsive polyion complex vesicles (PICsomes) are developed, bridging inflammation-instructed cfDNA scavenging, and methotrexate (MTX) delivery for AID management. A positively charged, PEGylated polypeptide with guanidine side chains (PEG-PG) is developed, which self-assembles with a negatively charged, cis -aconitic anhydride-modified poly- L -lysine (PC) to form the PICsomes and encapsulate MTX disodium salt. The neutrally charged PICsomes feature prolonged blood circulation after systemic administration, allowing for passive accumulation to the inflamed tissues. In the slightly acidic inflammatory microenvironment, PC transforms from negatively charged to positively charged, thereby disintegrating the PICsomes and liberating the PEG-PG and MTX. Consequently, PEG-PG-mediated cfDNA scavenging and MTX-mediated immunosuppression cooperate to inhibit inflammation and ameliorate the inflammatory microenvironment, promoting tissue repair in AID mouse models including collagen-induced arthritis and 2,4,6-trinitrobenzenesulfonic acid-induced colitis.

A balanced inflammatory response is crucial for the organism to defend against external infections, however, an exaggerated response may lead to detrimental effects, including tissue damage and even the onset of disease. Therefore, anti-inflammatory drugs are essential for the rational control of inflammation. In this study, we found that a previously screened peptide TaY (KEKKEVVEYGPSSYGYG) was able to inhibit the LPS-induced RAW264.7 inflammatory response by decreasing a series of proinflammatory cytokines, such as TNF-α, IL-6, and nitric oxide (NO). To elucidate the underlying mechanism, we conducted further investigations. Western blot analysis showed that TaY reduced the phosphorylation of key proteins (IKK-α/β, IκB-α,NF-κB (P65)) in the TLR4-NF-κB signaling pathway and inhibited the inflammatory response. Furthermore, molecular docking and molecular dynamic simulations suggested that TaY binds to the hydrophobic pocket of MD2 through hydrogen bonding and hydrophobic interactions, potentially competing with LPS for MD2 binding. Collectively, TaY is a promising candidate for the development of novel therapeutic strategies against inflammatory disorders.

Phthalimide and N-substituted phthalimide have a special structure that helps them to be pharmaceutically useful and biologically active. In this study, we investigated the antioxidant, anti-inflammatory and antibacterial effects of a synthetic phthalimide-containing derivative in an experimental asthma model. In vitro determination of antioxidant and chelating activity was carried out by spectrophotometric methods. The in vivo antioxidant activity was carried out in Wistar rats sensitized to ovalbumin in the experimental model of asthma. Our results reveal that that the synthesized N-sulfonylphthalimide molecule has a scavenging capacity against the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•) and a chelating activity on ferrous ions and revealed its protective capacity against altered markers of oxidative stress in the experimental asthma model. All the previous results were confirmed by the result of the histopathological study of the liver. Moreover, neo-synthesized N-sulfonylphthalimide 2 showed antibacterial activity against Gram-positive and Gram-negative bacteria with interesting MIC values. Finally, our study highlights the anti-inflammatory, anti-asthmatic and antibacterial effects of the N-sulfonylphthalimide molecule, which could potentially be a drug of choice in asthmatic pathology, especially during bacterial superinfections in the respiratory tract.

5,6-dihydroxyflavone (5,6-DHF), a flavonoid that possesses potential anti-inflammatory and antioxidant activities owing to its special catechol motif on the A ring. However, its function and mechanism of action against inflammation and cellular oxidative stress have not been elucidated. In the current study, 5,6-DHF was observed inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) and cytoplasmic reactive oxygen species (ROS) production with the IC 50 of 11.55 ± 0.64 μM and 0.8310 ± 0.633 μM in murine macrophages, respectively. Meanwhile, 5,6-DHF suppressed the overexpression of pro-inflammatory mediators such as proteins and cytokines and eradicated the accumulation of mitochondrial ROS (mtROS). The blockage of the activation of cell surface toll-like receptor 4 (TLR4), impediment of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 from the mitogen-activated protein kinases (MAPK) pathway, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) from the JAK-STAT pathway, and p65 from nuclear factor-κB (NF-κB) pathways were involved in the process of 5,6-DHF suppressing inflammation. Furthermore, 5,6-DHF acted as a cellular ROS scavenger and heme-oxygenase 1 (HO-1) inducer in relieving cellular oxidative stress. Importantly, 5,6-DHF exerted more potent anti-inflammatory activity than its close structural relatives, such as baicalein and chrysin. Overall, our findings pave the road for further research on 5,6-DHF in animal models.

Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates N-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through in vitro studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is considerable interest in the utilisation of plants against inflammation. Over 50 species of the plant family Amaryllidaceae are known for such usage in traditional medicine. This review was undertaken to identify the chemical principles responsible for these anti-inflammatory effects. It describes the findings from in vitro, in vivo and in silico studies, as well as the probes made on the mechanisms of action. The literature search returned over 600 hits, of which around 130 were chosen for their relevance to the text. Over 140 compounds have thus far been screened for anti-inflammatory effects. These were mostly isoquinoline alkaloids but also included other classes of secondary metabolites such as chromones, flavonoids and triterpenoids. In vitro studies were carried out in mononuclear cells such as lymphocytes, monocytes, neutrophils and macrophages, against which no serious side effects were observed. The constituents were also effective against inflammation induced by physical and chemical stimuli in a variety of murine test subjects. Chief among the compounds were the isoquinoline alkaloids lycorine and narciclasine, which displayed potent effects against pain, swelling, asthma and arthritis, amongst others. From a mechanistic perspective, several of the compounds were shown to mediate in inflammatory pathways, notably via the modulation of both pro-inflammatory (such as NF- κ B, TNF- α and IL-1) and anti-inflammatory (such as IL-10 and TGF- β ) factors. Useful insights also emerged from active-site docking studies of some of the compounds. The Amaryllidaceae affords a rich and diverse platform for the discovery of potential anti-inflammatory drugs., Competing Interests: The authors declare that they have no conflict of interest. The account herein is the product of findings made independently by the authors, no part of which may be deemed liable to any other individual or organisation., (Thieme. All rights reserved.)

Water buffalo horn (WBH), a traditional Chinese medicine, is known for its antipyretic, anti-inflammatory and antioxidant properties. This study aims to investigate the therapeutic potential of WBH keratin (WBHK) and its derived thiol-rich peptide fractions (SHPF) for oxidative stress and inflammation. WBHK and SHPF were prepared and tested using various models including LPS-induced fever in rabbits, H 2 O 2 -induced oxidative damage in bEnd.3 cells, TNF-α-induced inflammation in bEnd.3 cells and LPS-induced inflammation in RAW 264.7 cells. Expression of key markers, such as Nrf2, Hmox-1 and NF-κB, were analyzed using qRT-PCR, ELISA and Western blotting. Label-free quantitative proteomic analysis was used to identify key differential proteins associated with the efficacy of SHPF. Our results demonstrated that treatment with WBHK significantly reduced body temperature after 0.5 h of administration in the fever rabbit model. SHPF could alleviate cellular inflammatory injury and oxidative damage by activating the key transcription factor Nrf2 and increasing the expression level of Hmox-1. SHPF could inhibit the NF-κB pathway by reducing IκB phosphorylation. It was also found that SHPF could reduce pro-inflammatory cytokine (IL-6, COX-2 and PGE 2 ) and inhibit the expression of VCAM-1, ICAM-1, IL-6 and MCP-1. Proteomics analysis showed that SHPF could inhibit HMGB1 expression and release. The results indicated that SHPF could significantly reduce inflammation and oxidative stress by regulating the Nrf2/Hmox-1 and NF-κB pathways. These findings suggest the potential therapeutic applications of WBH components in the treatment of oxidative stress and inflammation-related 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 Inc. All rights reserved.)

In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema.

KLEPTOSE ® CRYSMEB methylated cyclodextrin derivative displays less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases, linked in part to cholesterol complexation and immune response, however, its impact on inflammatory cascade pathways is not clear. Thus, the impact of KLEPTOSE ® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells under physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP ® Diversity PLUS ® panel. Finally, its anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE ® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects that were driven by the inhibition of pro-inflammatory cytokine secretion and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Additionally, it appeared that the mechanism of action of KLEPTOSE ® CRYSMEB seems to not be shared by other well-known anti-inflammatory molecules. Finally, KLEPTOSE ® CRYSMEB may have an anti-inflammatory impact, which could be due to its effect on receptors such as TLR or direct complexation with LPS or PGE2, and conversely, this methylated cyclodextrin could stimulate a pro-inflammatory response involving lipid mediators and on proteins involved in communication with immune cells, probably via interaction with membrane cholesterol.

Pomegranate is a notable source of nutrients, containing a considerable proportion of organic acids, polysaccharides, vitamins, fatty acids, and polyphenols such as flavonoids, phenolic acids, and tannins. It is also rich in nutritionally important minerals and chemical elements such as K, P, Na, Ca, Mg, and N. The presence of several bioactive compounds and metabolites in pomegranate has led to its incorporation into the functional food category, where it is used for its numerous therapeutic properties. Pomegranate's bioactive compounds have shown antioxidant, anti-inflammatory, and anticancer effects. Aging is a process characterized by the chronic accumulation of damages, progressively compromising cells, tissues, and organs over time. Inflammaging is a chronic, subclinical, low-grade inflammation that occurs during the aging process and is linked to many age-related diseases. This review aims to summarize and discuss the evidence of the benefits of pomegranate extract and its compounds to slow the aging processes by intervening in the mechanisms underlying inflammaging. These studies mainly concern neurodegenerative and skin diseases, while studies in other fields of application need to be more practical. Furthermore, no human studies have demonstrated the anti-inflammaging effects of pomegranate. In the future, supplementation with pomegranate extracts, polyphenols, or urolithins could represent a valuable low-risk complementary therapy for patients with difficult-to-manage diseases, as well as a valid therapeutic alternative for the topical or systemic treatment of skin pathologies.

Lathyrane-based diterpenoid is one of the critical bioactive elements of Euphorbia lathyris L., a widely used traditional Chinese medicine for the treatment of inflammation and infection. In this study, we introduced and evaluated seven synthetic or natural lathyrane-based diterpenoids with the same core structure but notable structural variations at specific positions, for their anti-inflammatory and gout-alleviating properties. There was no significant cytotoxicity below 10 μM among the initial test of the cell counting kit 8 of the seven candidate derivatives (compounds 13 to 19) in this work. Furthermore, maintaining the acyloxy group at 15-C position and the strongly hydrophobic aryl structure at 3-C and 5-C positions, compounds 15 (Euphorbia factor L3, EFL3) and 17 strikingly inhibited the production of IL-1β related to the actuation of the inflammasome in our study. The ELISA assay indicated that the anti-inflammatory effects of EFL3 were better associated with MSU stimulation than other second-line pathways triggered by inflammasome. Further examinations on the acute paw gout model in C57BL/6 mice showed that EFL3 had a significantly inflammatory retarding effect by intraperitoneal injection. It decreased swelling volume as well as the cleavage and activation of local IL-1β and casepas-1 in the paw. To conclude, our findings reveal several potential key structure-activity relationships that govern the anti-inflammatory effects of lathyrane-type diterpenoids, the dispensable acyl group at the 15-C position, the importance of maintaining the spatial structure of the B-ring, and the potential importance of hydrophobic substituents at the 3-C position. These insights may provide guidance for the structural design of lathyrane-type agents in the future; furthermore, we found that the lathyrane-based diterpenoid EFL3 is a potential agent for gout that is expected to provide a novel therapeutic strategy for inflammation intervention., 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.)

Inflammation plays a critical role in the development of numerous diseases. Cannabidiol (CBD), found in hemp, exhibits significant pharmacological activities. Accumulating evidence suggests that CBD has anti-inflammatory and cardiovascular protection effects, but the potential mechanisms require further exploration. In this study, we aimed to reveal the mechanisms of CBD against high-fat, high-cholesterol (HFC) diet-induced inflammation combining metabolomics with network pharmacology. First, plasma lipidomics results indicated that oxidized lipids could serve as potential biomarkers for HFC diet-induced inflammation, and CBD reversed the elevated levels of oxidized lipids. The HFC diet was also found to enhance intestinal permeability, facilitating the entry of lipopolysaccharides (LPSs) into the circulatory system and subsequently increasing systemic inflammation. Additionally, cell metabolomic results indicated that CBD could reverse 10 important differential metabolites in LPS-induced RAW 264.7 cells. Using network pharmacology, we identified 49 core targets, and enrichment analysis revealed that arachidonic acid was the most significantly affected by CBD, which was closely associated with inflammation. Further integrated analysis focused on three key targets, including PTGS2, ALOX5, and ALOX15. Molecular docking showed high affinities between key targets and CBD, and qPCR further demonstrated that CBD could reverse the mRNA expression of these key targets in RAW 264.7 cells. Collectively, this finding integrates lipidomics and metabolomics with network pharmacology to elucidate the anti-inflammatory effects of CBD and validates key therapeutic targets.

Inflammation involves complex immune responses where cytokines such as TNF-α, IL-1, and IL-6 promote vasodilation and increased vascular permeability to facilitate immune cell migration to inflammation sites. Persistent inflammation is linked to diseases like cancer, arthritis, and neurodegenerative disorders. Although oral anti-inflammatory drugs are favored for their non-invasiveness and cost-effectiveness, their efficacy is often compromised due to gastrointestinal degradation and limited bioavailability. Recent advancements highlight the potential of extracellular vesicles (EVs) as nanocarriers that enhance drug delivery by encapsulating therapeutic agents, ensuring targeted release and reduced toxicity. These EVs, derived from dietary sources and cell cultures, exhibit excellent biocompatibility and stability, presenting a novel approach in anti-inflammatory therapies. This review discusses the classification and advantages of orally administered EVs (O-EVs), their mechanism of action, and their emerging role in treating inflammatory conditions, positioning them as promising vectors in the development of innovative anti-inflammatory drug delivery systems., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Zeng et al.)

Itaconic acid and its derivative 4-octyl itaconate (OI) represent a novel anti-inflammatory medication that has demonstrated efficacy in multiple inflammation models because of its minimal side effects. Recently, natural polymers conjugated with small molecule drugs, known as polymer-drug conjugates (PDCs), have emerged as a promising approach to sustained drug release. In this work, we reported an approach to prepare a PDC containing an OI and make it into an injectable hydrogel. Chitosan (CS) was selected for PDC synthesis because of its abundant free amino groups that can be conjugated with molecules containing carboxyl groups by carbodiimide chemistry. We used an ethanol/water cosolvent system to synthesize a CS-OI conjugate via EDC/NHS catalysis. The CS-OI conjugate had improved water solubility and unique anti-inflammatory activity and did not show compromised antibacterial activity compared with unmodified CS. Beta-glycerophosphate (β-GP) cross-linked CS-OI hydrogel exhibited good injectability with sustainable OI release and effectively modulated inflammatory response in a rat model. Therefore, this study provides valuable insights into the design of PDC hydrogels with inflammatory modulatory properties.

Transient receptor potential vanilloid 1 protein (TRPV1) is expressed widely in skin and sensory neurons that contribute to pain/heat sensation in the human system. TRPV1 gene polymorphisms are susceptible to multiple diseases and it is considered a therapeutic target for various inflammatory conditions. Among the TRPV1 variants, rs8065080 (1911 A > G) plays a vital role in painful osteoarthritis and migraine. The presence of rs8065080 polymorphism may render drug efficacy. This study aimed to identify better antagonists against wild-type and variant TRPV1 that may help in the relief of pain/inflammation. We constructed suitable TRPV1 protein structures for wild-type and rs8065080 variant through a homology modelling approach. A total of 3363 anti-inflammatory compounds with high chemical diversity and good drug-like properties were collected and screened against the generated structures. Molecular docking showed that nobilamide B had the highest binding affinity (-5.83 kcal/mol) towards the wild-type. Whereas, isoquinoline analogue displayed highest binding potency with the variant TRPV1 (-11.65 kcal/mol). Besides those, C18H15F3N4O showed affinity towards both wild-type (-5.53 kcal/mol) and variant TRPV1 (-9.75 kcal/mol). Then, molecular dynamic simulation revealed stable conformation in wild-type and variant TRPV1 upon binding of nobilmaide B, isoquinoline analogue and C18H15F3N4O. Additionally, density functional theory (DFT) using B3LYP hybrid function showed high chemical reactiveness of nobilamie B, isoquinoline analogue and C18H15F3N4O. Overall, our systematic investigations provide, C18H15F3N4O could be a potential analgesic inhibiting both wild-type and variant TRPV1 against inflammatory conditions.