Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo.

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.

Nanoparticle Encapsulation of the Hexane Fraction of Cyperus Rotundus Extract for Enhanced Antioxidant and Anti-Inflammatory Activities in vitro.

Aim: Cyperus rotundus L. (CR) is traditionally used in medicine for its anti-inflammatory properties. In particular, α-cyperone, which is isolated from the essential oil and found primarily in the n-hexane fraction of the ethanolic extract, is known to inhibit NO production in LPS-stimulated RAW 264.7 cells. However, high concentrations of α-cyperone are required for sufficient anti-inflammatory activity. Even, essential oil obtained from C. rotundus has the disadvantage of low solubility and stability in aqueous environment, which makes it difficult to be applied in various fields and easily loses its activity. Therefore, in this study, we aimed to increase the extraction yield of C. rotundus by microbubble extraction and prepare nanoparticles (NPs) that can preserve its activity in a stable and bioavailable manner by utilizing nanoprecipitation. Methods: C. rotundus rhizomes were extracted in 50% ethanol using microbubbles and then fractionated with n-hexane to obtain α-cyperone-rich C. rotundus n-hexane fraction (CRHF). The biodegradable plant extract, α-cyperone, was prepared as green nanoparticles (CR@NPs) by nanoprecipitation technique under mild reaction conditions. The physicochemical properties of CR@NPs, including size, polydispersity index, and surface charge, were determined using dynamic light scattering. The extraction yield and encapsulation efficiency of α-cyperone were quantified by high-performance liquid chromatography. Antioxidant and anti-inflammatory activities were evaluated by DPPH assay and in vitro ROS and NO assays, and biocompatibility was assessed by MTT assay. Results: C. rotundus loaded nanoparticles demonstrated overcoming the limitation of α-cyperone solubility and stability in CRHF and also the antioxidant, anti-inflammatory properties as evidenced by in vitro assays in cellular models. Conclusion: The versatility of green chemistry, such as α-cyperone, enables the production of nanoparticles with promising biomedical applications such as cosmetics, pharmaceuticals, and food products.

Acid-sensitive prodrugs; a promising approach for site-specific and targeted drug release.

Drugs administered through conventional formulations are devoid of targeting and often spread to various undesired sites, leading to sub-lethal concentrations at the site of action and the emergence of undesired effects. Hence, therapeutic agents should be delivered in a controlled manner at target sites. Currently, stimuli-based drug delivery systems have demonstrated a remarkable potential for the site-specific delivery of therapeutic moieties. pH is one of the widely exploited stimuli for drug delivery as several pathogenic conditions such as tumor cells, infectious and inflammatory sites are characterized by a low pH environment. This review article aims to demonstrate various strategies employed in the design of acid-sensitive prodrugs, providing an overview of commercially available acid-sensitive prodrugs. Furthermore, we have compiled the progress made for the development of new acid-sensitive prodrugs currently undergoing clinical trials. These prodrugs include albumin-binding prodrugs (Aldoxorubicin and DK049), polymeric micelle (NC-6300), polymer conjugates (ProLindac™), and an immunoconjugate (IMMU-110). The article encompasses a broad spectrum of studies focused on the development of acid-sensitive prodrugs for anticancer, antibacterial, and anti-inflammatory agents. Finally, the challenges associated with the acid-sensitive prodrug strategy are discussed, along with future directions.

Investigation of the phytochemical profiling and antioxidant, anti-diabetic, anti-inflammatory, and MDA-MB-231 cell line antiproliferative potentials of extracts from Ephedra alata Decne.

Ephedra is one of the many medicinal herbs that have been used as folk/traditional medicine in Jordan and other countries to cure various illnesses. Plants of this genus are well known for their antioxidant and antibacterial properties. In this study, three different solvents were used to obtain Ephedra extracts. When evaluated, the Ephedra alata Decne ethanolic extract reportedly had the greatest levels of total phenolic compounds (TPC) and total flavonoid compounds (TFC). The aqueous extracts displayed the highest antioxidant activity in the DPPH and ABTS assays, demonstrating their considerable capacity to neutralize free radicals. However, when evaluated using the FRAP method, the acetone extracts showed the strongest antioxidant activity, indicating their high reducing power. LC-MS/MS, a potent method of analysis that combines the liquid chromatographic separation properties with mass spectrometry detection and identification capabilities, was used in this study to detect and measure phytochemical content of a total of 24 phenolic compounds and 16 terpene compounds present in the extracts of Ephedra alata Decne. Various concentrations of these chemicals were found in these extracts. The extracts' inhibitory effects on albumin denaturation and alpha-amylase activity were also assessed; the findings demonstrated the potentials of these extracts as anti-inflammatory and anti-diabetic medicines, with the acetone extract having the lowest IC50 values in the concomitant tests (306.45 µg/ml and 851.23 µg/ml, respectively). Furthermore, the lowest IC50 value (of 364.59 ± 0.45 µg/ml) for the 80% ethanol extract demonstrated that it has the strongest antiproliferative impact regarding the MDA-MB-231 breast cancer cell line. This finding indicates that this particular extract can be potentially used to treat cancer.

Characterization and antioxidant activity of nano-formulated berberine and cyperus rotundus extracts with anti-inflammatory effects in mastitis-induced rats.

Bovine mastitis caused by infectious pathogens, mainly Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), constitutes a major destructive challenge for the dairy industry and public health. Berberine chloride (BER) and Cyperus rotundus possess a broad spectrum of anti-inflammatory, antioxidant, antibacterial, and antiproliferative activities; however, their bioavailability is low. This research aimed first to prepare an ethanolic extract of Cyperus rotundus rhizomes (CRE) followed by screening its phytochemical contents, then synthesis of BER and CRE loaded chitosan nanoparticles (NPs) (BER/CH-NPs and CRE/CH-NPs), afterward, the analysis of their loading efficiency in addition to the morphological and physicochemical characterization of the formulated NPs employing Scanning Electron Microscopy (SEM), Zeta Potential (ZP), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) assessments compared to their crude forms to evaluate the enhancement of bioavailability and stability. Isolation of bacterial strains from the milk of mastitic cows, used for induction of mammary gland (MG) inflammation in female albino rats, and a preliminary investigation of the prophylactic oral doses of the prepared NPs against S. aureus-induced mastitis in female rats. The minimal inhibitory concentration (MIC) of BER/CH-NPs and CRE/CH-NPs is 1 mg/kg b.w. BER/CH-NPs and CRE/CH-NPs alone or in combination show significant (P ≤ 0.05) DPPH radical scavenging activity (69.2, 88.5, and 98.2%, respectively) in vitro. Oral administration of BER/CH-NPs and CRE/CH-NPs to mastitis rats significantly (P ≤ 0.05) attenuated TNF-α (22.1, 28.6 pg/ml), IL-6 (33.4, 42.9 pg/ml), IL-18 (21.7, 34.7 pg/ml), IL-4 (432.9, 421.6 pg/ml), and MPO (87.1, 89.3 pg/ml) compared to mastitis group alongside the improvement of MG histopathological findings without any side effect on renal and hepatic functions. Despite promising results with BER and CRE nanoparticles, the study is limited by small-scale trials, a focus on acute administration, and partially explored nanoparticle-biological interactions, with no economic or scalability assessments. Future research should address these limitations by expanding trial scopes, exploring interactions further, extending study durations, and assessing economic and practical scalability. Field trials and regulatory compliance are also necessary to ensure practical application and safety in the dairy industry. In conclusion, the in vitro and in vivo results proved the antioxidant and anti-inflammatory efficacy of BER/CH-NPs and CRE/CH-NPs in low doses with minimal damage to the liver and kidney functions, supposing their promising uses in mastitis treatment.

Antioxidant and Anti-Inflammatory Capacities of Three Dry Bean Varieties after Cooking and In Vitro Gastrointestinal Digestion.

The present study delved into the chemical composition, antioxidant, and anti-inflammatory properties of three dry edible beans: Black (BL), Great Northern (GN), and Pinto (PN). The beans were soaked, cooked, and subjected to in vitro gastrointestinal (GI) digestion. BL bean exhibited significantly higher gastric (42%) and intestinal (8%) digestion rates. Comparative assessment of soluble GI-digested fractions (<3 kDa) revealed that the GN bean exhibited the highest abundance of dipeptides (P < 0.05). The BL bean fraction displayed a 4-fold increase in tripeptides (P < 0.05). Both BL and PN bean fractions are high in essential free amino acids, flavonols, and derivatives of hydroxybenzoic acid when compared to the GN bean. All the beans exhibited the ability to mitigate TNF-α-induced pro-inflammatory signaling; however, the BL bean fraction was the most effective at lowering AAPH-induced oxidative stress in HT-29 cells, followed by the GN bean (P < 0.05). In contrast, a low antioxidant effect was observed with PN beans.

Antibacterial, Anti-Inflammatory, and Antioxidant Cotton-Based Wound Dressing Coated with Chitosan/Cyclodextrin-Quercetin Inclusion Complex Nanofibers.

Quercetin, recognized for its antioxidant, anti-inflammatory, and antibacterial properties, faces limited biomedical application due to its low solubility. Cotton, a preferred wound dressing material over synthetic ones, lacks inherent antibacterial and wound-healing attributes and can benefit from quercetin features. This study explores the potential of overcoming these challenges through the inclusion complexation of quercetin with cyclodextrins (CDs) and the development of a nanofibrous coating on a cotton nonwoven textile. Hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) formed inclusion complexes of quercetin, with chitosan added to enhance antibacterial properties. Phase solubility results showed that inclusion complexation can enhance quercetin solubility up to 20 times, with HP-γ-CD forming a more stable inclusion complexation compared with HP-ß-CD. Electrospinning of the nanofibers from HP-ß-CD/Quercetin and HP-γ-CD/Quercetin aqueous solutions without the use of a polymeric matrix yielded a uniform, smooth fiber morphology. The structural and thermal analyses of the HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers confirmed the presence of inclusion complexes between quercetin and each of the CDs (HP-ß-CD and HP-γ-CD). Moreover, HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers showed a near-complete loading efficiency of quercetin and followed a fast-releasing profile of quercetin. Both HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers showed significantly higher antioxidant activity compared to pristine quercetin. The HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers also showed antibacterial activity, and with the addition of chitosan in the HP-γ-CD/Quercetin system, the Chitosan/HP-γ-CD/Quercetin nanofibers completely eliminated the investigated bacteria species. The nanofibers were nontoxic and well-tolerated by cells, and exploiting the quercetin and chitosan anti-inflammatory activities resulted in the downregulation of IL-6 and NO secretion in both immune as well as regenerative cells. Overall, CD inclusion complexation markedly enhances quercetin solubility, resulting in a biofunctional antioxidant, antibacterial, and anti-inflammatory wound dressing through a nanofibrous coating on cotton textiles.

Natural harmaline acts as novel fluorescent probe for hypochlorous acid and promising therapeutic candidate for rheumatoid arthritis.

Endogenous hypochlorous acid (HOCl) is one of the most important reactive oxygen species (ROS) and acts as a distinct biomarker that is involved in various inflammatory responses including rheumatoid arthritis (RA). Therefore, it's crucial to develop an efficient method for the tracking and analysis of HOCl levels in vivo. Natural products continue to be compounds of interest, because they not only offer diverse and specific molecular scaffolds but also provide invaluable sources for new drug discovery. Herein, we firstly demonstrated harmaline (HML), a natural alkaloid mainly found in Peganum harmala L, could be acted as a novel fluorescent probe for HOCl with exceptional precision and responsiveness. Remarkably, this probe not only specifically tracked HOCl levels in cells and inflammatory RA mouse models, but also exhibited effective anti-inflammatory effects on RAW264.7 cells and anti-proliferative effects on fibroblast-like synoviocytes. Furthermore, HML has the potential to alleviate LPS-induced inflammation by inhibiting the NF-κB signaling pathway. This study represents the first example of a natural product that can simultaneously act as a fluorescent probe for specific ROS and a promising therapeutic candidate for a specific disease, which will undoubtedly extend the application of fluorophore-rich natural products.

Benzimidazole-Oxadiazole Hybrids-Development in Medicinal Chemistry: An Overview.

To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety's potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole-oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti-inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole-oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure-activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole-oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes.

Chitosan/rutin multifunctional hydrogel with tunable adhesion, anti-inflammatory and antibacterial properties for skin wound healing.

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.

Total Synthesis and Anti-inflammatory Activity of Asperjinone and Asperimide C.

Total syntheses of two γ-butenolide natural products, asperjinone (1) and asperimide C (2) in both racemic and chiral forms have been accomplished utilizing Basavaiah's one-pot Friedel-Crafts/maleic anhydride formation protocol as a key strategy. Our syntheses verified the revised structure of 1 proposed by Williams et al. and the structure and absolute configuration of 2 reported by the Li group. This work also discloses the unprecedented anti-inflammatory activity of 1. Synthetic 1 exhibited significant anti-inflammatory activity in renal proximal tubular epithelial cells (RPTEC) by suppression of gene expression of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 under LPS-induced renal inflammation condition and was superior to (S)-1, rac-2, 2, and a positive drug control, indomethacin. Moreover, compound 1 inhibited downstream signaling of inflammation by significantly reducing iNOS and COX-2 gene expression and total NO production. The anti-inflammatory activity of asperjinone (1) renders it a potential and promising candidate for developing novel anti-inflammatory agents against inflammation worsening acute kidney injury.

An integrated network pharmacology and molecular docking approach to reveal the role of Arctigenin against Cutibacterium acnes-induced skin inflammation by targeting the CYP19A1.

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.

Anti-Inflammatory Potential of Pygeum africanum Bark Extract: An In Vitro Study of Cytokine Release by Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells.

Pygeum africanum bark has been shown to inhibit the production of pro-inflammatory prostaglandins in the prostate and reduces the production of leukotrienes and other 5-lipoxygenase (5-LO) metabolites. It has been suggested that inflammation plays an important role in the pathophysiology of benign prostatic hyperplasia (BPH). Data from clinical trials have shown that P. africanum improves the symptoms and objective measures of BPH. This in vitro study aimed to assess the anti-inflammatory potential of a proprietary Pygeum bark standardized extract (Prunera®) on cytokine release from lipopolysaccharide-stimulated human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from four donors, and a bead-based assay (ProcartaPlex™ panel) was used for the detection and quantitation of cytokines. Pygeum africanum bark standardized extract (PABE) induced a statistically significant decrease (p < 0.05) of IL-6 in three donors. Other effects were as follows: IL-2 was lowered in all donors in the absence of a clear dose-response relationship; IL-4, IL-5, IL-9, and IL-13 levels were decreased in most donors; IL-22 levels seemed to be suppressed only for donor 4 at lower and medium concentrations; and IL-27 and TNF-α levels decreased at all PABE concentrations in all donors. The anti-inflammatory effect of PABE, particularly the reduction in IL-6 as a marker of inflammation, supports the potential use of this natural compound in the management of BPH and other conditions in which pro-inflammatory cytokines are involved in their underlying pathophysiological mechanisms.

Cathepsin B-Activatable Bioactive Peptide Nanocarrier for High-Efficiency Immunotherapy of Asthma.

Introduction: Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma. Methods: MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining. Results: In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg). Discussion: Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.

Synthesis and Biological Evaluation of Novel Chlorogenic Acid-Apigenin Conjugates as Anti-acute Gout Agents.

Gout is the second largest metabolic disease worldwide after diabetes, with acute gouty arthritis as most common symptom. Xanthine oxidase (XOD) and the NOD like receptor-3 (NLRP3) inflammasome are the key targets for acute gout treatment. Chlorogenic acid has been reported with a good anti-inflammatory activity, and Apigenin showed an excellent potential in XOD inhibition. Therefore, a series of chlorogenic acid-apigenin (CA) conjugates with varying linkers were designed and synthesized as dual XOD/NLRP3 inhibitors, and their activities both in XOD and NLRP3 inhibition were evaluated. An in vitro study of XOD inhibitory activity revealed that the majority of CA conjugates exhibited favorable XOD inhibitory activity. Particularly, the effects of compounds 10c and 10d, with an alkyl linker on the apigenin moiety, were stronger than that of allopurinol. The selected CA conjugates also demonstrated a favorable anti-inflammatory activity in RAW264.7 cells. Furthermore, compound 10d, which showed the optimal activity both in XOD inhibition and anti-inflammatory, was chosen and its inhibitory ability on NLRP3 and related proinflammatory cytokines was further tested. Compound 10d effectively reduced NLRP3 expression and the secretion of interluekin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) with an activity stronger than the positive control isoliquiritigenin (ISL). Based on these findings, compound 10d exhibits dual XOD/NLRP3 inhibitory activity and, therefore, the therapeutic effects on acute gout is worthy of further study.

Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3.

Soluble transforming growth factor beta receptor 3 (sTGFBR3) antagonist is a new focus in the research and development of Alzheimer's disease (AD) drugs. Our previous studies have identified sTGFBR3 as a promising new target for AD, with few targeted antagonists identified. In this study, we performed structural modeling of sTGFBR3 using AlphaFold2, followed by high-throughput virtual screening and surface plasmon resonance assays. which collectively identified Xanthone as potential compounds for targeting sTGFBR3. After optimizing the sTGFBR3-Xanthone complex using molecular dynamics (MD) simulations, we prepared a series of novel Xanthone derivatives and evaluated their anti-inflammatory activity, toxicity, and structure-activity relationship in BV2 cell model induced by lipopolysaccharides (LPS) or APP/PS1/tau mouse brain extract (BE). Several derivatives with the most potent anti-inflammatory activity were tested for blood-brain barrier permeability and sTGFBR3 affinity. Derivative P24, selected for its superior properties, was further evaluated in vitro. The results indicated that P24 increased the activation of TGF-ß signaling and decreased the activation of IκBα/NF-κB signaling by targeting sTGFBR3, thereby regulating the inflammation-phagocytosis balance in microglia. Moreover, the low acute toxicity, long half-life, and low plasma clearance of P24 suggest that it can be sustained in vivo. This property may render P24 a more effective treatment modality for chronic diseases, particularly AD. The study demonstrates P24 serve as potential novel candidates for the treatment of AD via antagonizing sTGFBR3.

The effect of Jordanian essential oil from coriander seeds on antioxidant, anti-inflammatory, and immunostimulatory activities using RAW 246.7 murine macrophages.

Coriander (Coriandrum sativum L.) is a member of the Umbelliferae/Apiaceae family and one of the well-known essential oil-containing plants, in which the seeds are used in traditional medicine, and as flavoring in food preparation. Knowing the diverse chemical components of different parts of the plant, this work aims to investigate the antioxidant, the anti-inflammatory, and the immunostimulatory modulator effects of the Jordanian C. sativum's seed extracted essential oil (JCEO). Coriander oil extract was prepared by hydro-distillation method using the Clevenger apparatus. Different concentrations of coriander oil were examined by using DPPH radical scavenging assay, MTT assay, pro-inflammatory cytokine (Tumor Necrosis Factor-TNF-alpha) production in RAW264.7 murine macrophages in addition, scratch-wound assessment, NO level examination, Th1/Th2 assay, phagocytosis assay, and fluorescence imaging using DAPI stain were conducted. JCEO had a potential metabolic enhancer effect at a concentration of 0.3 mg/mL on cell viability with anti-inflammatory activities via increasing cytokines like IL-10, IL-4, and limiting NO, INF-γ, and TNF-α release into cell supernatant. Antioxidant activity was seen significantly at higher concentrations of JCEO reaching 98.7% when using 100mg/mL and minimally reaching 50% at 12.5mg/mL of the essential oil. Treated macrophages were able to attain full scratch closure after 48-hrs at concentrations below 0.3mg/mL. The seed-extracted JCEO showed significant free radical scavenging activity even at lower dilutions. It also significantly induced an anti-inflammatory effect via an increase in the release of cytokines but reduced the LPS-induced NO and TNF-α production at 0.16-0.3mg/mL. In summary, coriander essential oil demonstrated antioxidant, anti-inflammatory, and immunostimulatory effects, showcasing its therapeutic potential at specific concentrations. The findings underscore its safety and metabolic enhancement properties, emphasizing its promising role in promoting cellular health.

Magnetic nanoparticle-based combination therapy: Synthesis and in vitro proof of concept of CrFe2O4- rosmarinic acid nanoparticles for anti-inflammatory and antioxidant therapy.

Magnetic drug delivery systems using nanoparticles present a promising opportunity for clinical treatment. This study explored the potential anti-inflammatory properties of RosA- CrFe2O4 nanoparticles. These nanoparticles were developed through rosmarinic acid (RosA) co-precipitation via a photo-mediated extraction technique. XRD, FTIR, and TEM techniques were employed to characterize the nanoparticles, and the results indicated that they had a cubic spinel ferrite (FCC) structure with an average particle size of 25nm. The anti-inflammatory and antioxidant properties of RosA- CrFe2O4 nanoparticles were evaluated by using LPS-induced raw 264.7 macrophages and a hydrogen peroxide scavenging assay, respectively. The results showed that RosA- CrFe2O4 nanoparticles had moderate DPPH scavenging effects with an IC50 value of 59.61±4.52µg/ml. Notably, these nanoparticles effectively suppressed the expression of pro-inflammatory genes (IL-1ß, TNF-α, IL-6, and iNOS) in LPS-stimulated cells. Additionally, the anti-inflammatory activity of RosA- CrFe2O4 nanoparticles was confirmed by reducing the release of secretory pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated macrophages. This investigation highlights the promising potential of Phyto-mediated CrFe2O4-RosA as an anti-inflammatory and antioxidant agent in biomedical applications.

Marine Polyphenols in Cardiovascular Health: Unraveling Structure-Activity Relationships, Mechanisms, and Therapeutic Implications.

Cardiovascular diseases (CVDs) are responsible for significant mortality rates globally that have been raised due to the limitation of the available treatments and prevalence of CVDs. The innovative research and identification of potential preventives for CVDs are essential to alleviate global deaths and complications. The marine environment is a rich source of bioactive substances and provides a unique chemical arsenal against numerous ailments due to its unrivaled biodiversity. Marine polyphenolic compounds (MPCs) are unique because of their structural variety and biologically significant activity. Further, MPCs are well-reported for their valuable biological activities, such as anti-inflammatory, cardioprotective, and antioxidant, demonstrating encouraging results in preventing and treating CVDs. Therefore, investigation of the structure-activity relationship (SAR) between MPCs and CVDs provides insights that reveal how the structural components of these compounds affect their effectiveness. Further, comprehending this correlation is essential for advancing medications and nutraceuticals sourced from marine sources, which could transform the strategy for treating and preventing cardiovascular diseases. Therefore, this study provides a comprehensive analysis of existing research by emphasizing the role of MPCs in CVD treatments and evaluating the SAR between MPCs and CVDs with challenges and future directions.

Comparative In Vitro Study between Biocompatible Chitosan-Based Magnetic Nanocapsules and Liposome Formulations with Potential Application in Anti-Inflammatory Therapy.

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.