Synergistic Anti-inflammatory Effect Research Articles

Novel poly(lactic-co-glycolic acid) nanoliposome-encapsulated diclofenac sodium and celecoxib enable long-lasting synergistic treatment of osteoarthritis.

Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL. PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL. The particle size of PPLs-DS-CEL was 218.36 ± 6.27nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties. This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems.

Inflammatory macrophage reprogramming strategy of fucoidan microneedles-mediated ROS-responsive polymers for rheumatoid arthritis

During the pathogenesis of rheumatoid arthritis, inflammatory cells usually infiltrate synovial tissues, notably, M1-type macrophages, whose redox imbalance leads to the degradation of joint structures and deterioration of function. Natural active products play a vital role in immune modulation and antioxidants. In this study, we constructed a ROS-responsive nanoparticle called FTL@SIN, which consists of fucoidan (Fuc) and luteolin (Lut) connected by a ROS-responsive bond, Thioketal (TK), and encapsulated with an anti-rheumatic drug, Sinomenine (SIN), for synergistic anti-inflammatory effects. The FTL@SIN is then dispersed in high molecular weight Fuc-fabricated dissolvable microneedles (FTL@SIN MNs) for local administration. Therapy of FTL@SIN MNs afforded a significant decrease in macrophage inflammation while decreasing key pro-inflammatory cytokines and repolarizing M1 type to M2 type, thereby ameliorating synovial inflammation, and promoting cartilage repair. Additionally, our investigations have revealed that Fucoidan (Fuc) demonstrates synergistic effects, exhibiting superior mechanical strength and enhanced physical stability when compared to microneedles formulated solely with hyaluronic acid. This study combines nanomedicine with traditional Chinese medicine, a novel drug delivery strategy that presents a promising avenue for therapeutic intervention in rheumatoid arthritis.

Curcumin-loaded biomimetic nanosponges for osteoarthritis alleviation by synergistically suppressing inflammation and ferroptosis

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage while sustained inflammation and ferroptosis have been demonstrated to play crucial roles in the progression of OA. It is an effective strategy to fabricate nanomedicines for OA treatment. However, current research primarily concentrates on anti-inflammation, whereas nanomedicine systems for anti-ferroptosis in OA treatment are rarely reported. Additionally, there are few studies integrating inflammation inhibition with anti-ferroptosis within a single system to ameliorate OA progression. In this study, we introduce a curcumin-loaded biomimetic nanosponge (CM@Cur-NPs) to alleviate OA by synergistically suppressing inflammation and ferroptosis. CM@Cur-NPs were obtained by encapsulating curcumin within polymeric nanoparticles and coating them with macrophage cell membranes. The in vitro and in vivo synergistic anti-inflammatory and anti-ferroptotic effects of CM@Cur-NPs were investigated. It was discovered that the CM@Cur-NPs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), iNOS, ROS, and apoptosis levels of chondrocytes while concurrently increasing the anti-inflammatory cytokine (IL-4) and extracellular matrix (ECM) content in vitro. We also found that CM@Cur-NPs decreased the expression of the ferroptosis marker Fe2+, ACSL4, and MDA, coupled with an increase in the levels of SLC7A11 and GPX4 of chondrocytes. Lipid peroxidation of chondrocytes was attenuated by CM@Cur-NPs as well. In vivo results indicated that CM@Cur-NPs effectively alleviated OA progression and achieved cartilage protection by upregulating Aggrecan and collagen II expression, along with downregulating ADAMTS5 and MMP13 expression. This study demonstrated that CM@Cur-NPs exhibited enhanced chondroprotective effects through synergistic anti-inflammatory and anti-ferroptotic actions. It is a promising approach to integrate inflammation and ferroptosis inhibition by bioactive nanomaterials for OA treatment.

Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.

Cascade Reactions Catalyzed by Gold Hybrid Nanoparticles Generate CO Gas Against Periodontitis in Diabetes.

The treatment ofdiabetic periodontitis poses a significant challenge due to the presence of local inflammation characterized by excessive glucose concentration, bacterial infection, and high oxidative stress. Herein, mesoporous silica nanoparticles (MSN) are embellished with gold nanoparticles (Au NPs) and loaded with manganese carbonyl to prepare a carbon monoxide (CO) enhanced multienzyme cooperative hybrid nanoplatform (MSN-Au@CO). The Glucose-like oxidase activity of Au NPs catalyzes the oxidation of glucose to hydrogen peroxide (H2O2) and gluconic acid，and then converts H2O2 to hydroxyl radicals (•OH) by peroxidase-like activity to destroy bacteria. Moreover, CO production in response to H2O2, together with Au NPs exhibited a synergistic anti-inflammatory effect in macrophages challenged by lipopolysaccharides. The underlying mechanism can be the induction of nuclear factor erythroid 2-related factor 2 to reduce reactive oxygen species, and inhibition of nuclear factor kappa-B signaling to diminish inflammatory response. Importantly, the antibacterial and anti-inflammation effects of MSN-Au@CO are validated in diabetic rats with ligature-induced periodontitis by showing decreased periodontal bone loss with good biocompatibility. To summarize, MSN-Au@CO is fabricate to utilize glucose-activated cascade reaction to eliminate bacteria, and synergize with gas therapy to regulate the immune microenvironment, offering a potential direction for the treatment of diabetic periodontitis.

A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralensis against COPD

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited. PurposeThis study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy. Study design and methodsThe present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD. ResultsULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK. ConclusionThe combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.

CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain

Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.

Synergistic Antioxidant and Anti-Inflammatory Effects of Phenolic Acid-Conjugated Glutamine-Histidine-Glycine-Valine (QHGV) Peptides Derived from Oysters (Crassostrea talienwhanensis).

The glutamine-histidine-glycine-valine (QHGV), a peptide derived from oysters, exhibits antioxidant activity and is being actively researched as a potential pharmaceutical and functional cosmetic ingredient. In this study, we synthesized the QHGV peptide and explored the hitherto unknown anti-inflammatory effects of QHGV. The antioxidant property was also characterized by conjugating with various naturally derived phenolic acids, such as caffeic, gallic, ferulic, sinapinic, and vanillic acids. Conjugation with phenolic acids not only enhanced the antioxidant activity of QHGV but also diminished the lipopolysaccharide-induced generation of reactive oxygen species (ROS) in the murine macrophage cell line, RAW 264.7. The reduction in the levels of reactive oxygen species led to the reduced mRNA expression of inducible nitric oxide synthase (iNos) and cyclooxygenase 2 (Cox-2), resulting in an anti-inflammatory effect through the inhibition of the phosphorylation of mitogen-activated protein kinase, including extracellular signal-activated protein kinase, c-Jun NH2-terminal kinase, and p38. Furthermore, the phenolic acid-conjugated peptides increased the mRNA and protein levels of collagen type I, indicative of a wrinkle-improvement effect. The phenolic acid conjugates of the peptide were not cytotoxic to human keratinocytes such as HaCaT cells. These results suggest that phenolic acid conjugation can enhance the potential of peptides as drug and cosmetic resources.

Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions.

The undesirable inflammation and the excessive M1 macrophage activity may lead to inflammatory diseases. Corticosteroids and stem cell therapy are used in clinical practice to promote anti-inflammatory responses. However, this protocol has limitations and is associated with numerous side effects. In this study, the synergistic anti-inflammatory effects of dexamethasone (Dex) and mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) were evaluated to enhance the polarization of M1 inflammatory macrophages into the anti-inflammatory (M2) phenotype. Hence, we designed different combinations of Dex and EVs using three methods, including EVs isolated from Dex-preconditioned MSCs (Pre-Dex-EVs), EVs loaded with Dex (L-Dex-EVs), and EVs and Dex co-administration (Dex + EVs). All designed EVs had a significant effect on reducing the expression of M1-related genes (iNOS, Stat1, and IRF5), cytokines (IL6 and TNF-a), and CD markers (CD86) in lipopolysaccharide-stimulated macrophages. On the other hand, these combinations promoted the expression of alternative-activated M2-related genes (Arg-1, Stat6, and IRF4), cytokine (IL10), and CD markers (CD206).The combination of Dex and MSC-EVs enhances the effectiveness of both and synergistically promotes the conversion of inflammatory macrophages into an anti-inflammatory state.

Formulation and Evaluation of Herbal Emulsion-Based Gel Containing Combined Essential Oils from Melaleuca alternifolia and Citrus hystrix

Aims: This study aimed to investigate the synergistic anti-inflammatory effects of combined essential oils from Melaleuca alternifolia and Citrus hystrix peel. Methodology: An emulsion-based gel containing combined essential oils from Melaleuca alternifolia and Citrus hystrix peel was topically applied to the injected area of the carrageenan-induced hind paw edema mouse model. Diclofenac sodium was used as a positive control. The inhibition percentage of protein denaturation in all mice was assessed and calculated based on paw volume (Pv). Results: The highest inhibition percentage, recorded at the third hour in the carrageenan-induced hind paw edema mouse model, was 44.76%, achieved by the mice treated with combined essential oils. This was followed by diclofenac-treated (37.14%), tea tree essential oil-treated (27.62%), and kaffir lime peel essential oil-treated mice (20.10%). A similar trend was observed after 24 hours of treatment, with the anti-inflammatory activity of combined essential oils-treated mice recorded at 46.74%, followed by diclofenac-treated (35.87%), tea tree essential oil-treated (24.97%) and kaffir lime peel essential oil-treated mice (11.97%). Conclusion: These findings confirm the synergistic anti-inflammatory effects of the combined essential oils-incorporated emulsion-based gel on the carrageenan-induced hind paw edema mouse model.

Probiotic Consortium Confers Synergistic Anti-Inflammatory Effects in Inflammatory Disorders.

The composition and diversity of gut microbiota significantly influence the immune system and are linked to various diseases, including inflammatory and allergy disorders. While considerable research has focused on exploring single bacterial species or consortia, the optimal strategies for microbiota-based therapeutics remain underexplored. Specifically, the comparative effectiveness of bacterial consortia versus individual species warrants further investigation. In our study, we assessed the impact of the bacterial consortium MPRO, comprising Lactiplantibacillus plantarum HY7712, Bifidobacterium animalis ssp. lactis HY8002, and Lacticaseibacillus casei HY2782, in comparison to its individual components. The administration of MPRO demonstrated enhanced therapeutic efficacy in experimental models of atopic dermatitis and inflammatory colitis when compared to single strains. MPRO exhibited the ability to dampen inflammatory responses and alter the gut microbial landscape significantly. Notably, MPRO administration led to an increase in intestinal CD103+CD11b+ dendritic cells, promoting the induction of regulatory T cells and the robust suppression of inflammation in experimental disease settings. Our findings advocate the preference for bacterial consortia over single strains in the treatment of inflammatory disorders, carrying potential clinical relevance.

Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B0AT1

Sodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B0AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a protective role in the integrity of the intestinal barrier has been established. The natural ligands of SGLT1 (d-glucose) and of B0AT1 (l-glutamine) can trigger a protective anti-inflammatory effect on the intestinal epithelium. The literature suggests the activation of common intracellular pathways upon engagement of the two transporters, whose functional forms are composed of oligomers or clusters. Simultaneous activation of these two co-transporters could lead to a potential multitarget and synergistic anti-inflammatory effect. Therefore, nanoplatforms containing multiple copies of the ligands could represent chemical tools to study the potential simultaneous activation of the two co-transporters. For these reasons, in this study, a set of different gold nanoparticles decorated with derivatives of d-glucose and of l-glutamine were designed and prepared. In particular, the synthesis of suitable sulfur-ending functionalized ligand derivatives, including a C-glucoside derivative, their anchoring to gold nanoparticles and their physical–chemical characterization have been carried out. The obtained nanostructures could represent promising multifunctional platforms for further investigation of the existence of possible multitarget and synergistic effects toward the two co-transporters SGLT1 and B0AT1.

Resveratrol-loaded sulfated Hericium erinaceus β-glucan-chitosan nanoparticles: Preparation, characterization and synergistic anti-inflammatory effects

Resveratrol (RES) is a natural polyphenol with excellent biological activity. But the poor stability and bioavailability of RES severely limit its application. Thus, the resveratrol-loaded sulfated Hericium erinaceus β-glucan-chitosan nanoparticles (DS-CS-RES NPs) were prepared using electrostatic self-assembly to solve these problems in this study. The structure of DS-CS-RES NPs was spherical or sub spherical shape with small average particle size (191.07 nm), which was characterized by FT-IR, FS, XRD and TEM. DS-CS-RES NPs exhibited good stability and RES had a sustainable release from the nanoparticles in gastrointestinal digestion. Meanwhile, DS-CS-RES NPs could improve the inflammatory injury of LPS stimulated RAW264.7 macrophages by inhibiting the production of NO, IL-1β, IL-6 and TNF-α. Furthermore, DS-CS-RES NPs had strong anti-inflammatory activity by regulating protein levels of NF-κB p65, STAT1 and TLR4 through NF-κB and JAK-STAT1 signaling pathway in vitro, and sulfated H. erinaceus β-glucan-chitosan nanoparticle (DS-CS NPs) and RES had synergistic anti-inflammatory effect. Overall, DS-CS NPs can serve as a potential green and safe functional carrier for encapsulating resveratrol, which can improve its anti-inflammatory activity. This work may be conducive to the development of functional carrier for encapsulating RES and applications of hydrophobic active molecules in functional foods or medicines.

Investigation of the Therapeutic Effect of Salbutamol on Endometriosis in a Mouse Model.

Endometriosis is an immune chronic inflammatory disease, and there are currently no more effective drugs for treating endometriosis due to its unknown etiology. Salbutamol is a β2-adrenergic receptor (β2AR) agonist commonly used to treat asthma by selectively activating β2 receptors on airway smooth muscle and leukocytes, exerting bronchial dilation and synergistic anti-inflammatory effects. In recent years, β2AR agonists have been used in endometriosis studies, and we speculate that salbutamol may have a therapeutic effect on endometriosis. The purpose of this research was to explore the therapeutic effect of salbutamol on endometriosis mice. The mouse endometriosis model was established and treated with different doses of salbutamol. Endometrial lesions were harvested for pathological diagnosis, immunohistochemistry (IHC), Masson staining, and toluidine blue analysis. We found that the number and size of endometriotic lesions were all significantly decreased after 3 weeks of treatment with different doses of salbutamol on endometriosis model mice (P < 0.05). After Salbutamol treatment, the amount of mast cells (toluidine blue) and macrophages (F4/80) in the lesions as well as the expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-ɑ, platelet-derived growth factor subunit B (PDGFB), CD31, transforming growth factor (TGF)-β, Masson staining, BCL2, TUBB3, substance P (SP), and nerve growth factor (NGF) were significantly reduced (P < 0.05). These results suggested that salbutamol could effectively treat endometriosis in mice by reducing immune inflammatory cells and factors, angiogenesis, and fibrosis, increasing apoptosis of endometriotic lesions, and decreasing neurogenesis.

Synergistic antioxidant and anti-inflammatory effects of combined supplementation with oral zinc and dietary Moringa oleifera leaf in streptozotocin-induced diabetic rats

Individual interventions with zinc or M. oleifera leaf powder have shown some promise in managing diabetes-induced oxidative stress and inflammation. This study examined the synergistic effect of oral zinc and dietary M. oleifera leaf supplementation on the serum antioxidant and anti-inflammatory activities in streptozotocin-induced diabetic rats. Seven groups of 56 rats were used in the experiment: (1) normal rats + normal diet, (2) normal rats + 3% M. oleifera leaf-supplemented diet, (3) non-treated diabetic rats, (4) diabetic rats + 200 mg/kg metformin, (5) diabetic rats + 3% M. oleifera leaf-supplemented diet, (6) diabetic rats + 100 mg/kg oral zinc sulfate, and (7) diabetic rats + 3% M. oleifera leaf-supplemented diet + 100 mg/kg oral zinc sulfate. ELISA assay kits were used for antioxidant and anti-inflammatory markers respectively. The results suggest that when all treated diabetic groups were compared with non-treated diabetic control at p&lt;0.05, only groups 4 and 7 showed a significant increase in superoxide dismutase activity. Only group 5 showed a significant increase in reduced glutathione. No significant changes were observed in catalase and the total antioxidant capacity. MDA decreased significantly in group 7 only. There was a significant reduction in interleukin-6 in groups 6 and 7. Only group 7 showed significantly reduced C-reactive protein. Tumor necrosis factor-α reduced significantly in group 6 only. Overall, the combined supplementation with zinc and M. oleifera outperformed the individual treatments with either zinc or M. oleifera in ameliorating diabetes-induced oxidative stress and inflammation, indicating a possible synergistic effect of their combination.

Synergistic anti-oxidant and anti-inflammatory effects of ceria/resatorvid co-decorated nanoparticles for acute lung injury therapy

BackgroundAcute lung injury (ALI) is a critical inflammatory response syndrome that rapidly develops into acute respiratory distress syndrome (ARDS). Currently, no effective therapeutic modalities are available for patients with ALI/ARDS. According to recent studies, inhibiting both the release of pro-inflammatory cytokines and the formation of reactive oxygen species (ROS) as early as possible may be a promising therapy for ALI.ResultsIn this study, a ROS-responsive nano-delivery system based on oxidation-sensitive chitosan (Ox-CS) was fabricated for the simultaneous delivery of Ce NPs and RT. The in vitro experiments have shown that the Ox-CS/Ceria-Resatorvid nanoparticles (Ox-CS/CeRT NPs) were rapidly and efficiently internalised by inflammatory endothelial cells. Biological evaluations validated the significant attenuation of ROS-induced oxidative stress and cell apoptosis by Ox-CS/CeRT NPs, while maintaining mitochondrial function. Additionally, Ox-CS/CeRT NPs effectively inhibited the release of pro-inflammatory factors. After intraperitoneal (i.p.) administration, Ox-CS/CeRT NPs passively targeted the lungs of LPS-induced inflamed mice and released the drug activated by the high ROS levels in inflammatory tissues. Finally, Ox-CS/CeRT NPs significantly alleviated LPS-induced lung injury through inhibiting both oxidative stress and pro-inflammatory cytokine expression.ConclusionsThe created Ox-CS/CeRT NPs could act as a prospective nano-delivery system for a combination of anti-inflammatory and anti-oxidant therapy of ALI.Graphical

From co-delivery to synergistic anti-inflammatory effect: Studies on chitosan-stabilized Janus emulsions having chloroquine phosphate and flavopiridol in Complete Freund's Adjuvant induced arthritis rat model

For the first time, the co-delivery of chloroquine phosphate and flavopiridol by intra-articular route was achieved to provide local joint targeting in Complete Freund's Adjuvant-induced arthritis rat model. The presence of paired-bean structure onto the dispersed oil droplets of o/w nanosized emulsions allows efficient entrapment of two drugs (85.86–96.22 %). The dual drug-loaded emulsions displayed a differential in vitro drug release behavior, near normal cell viability in MTT assay, better cell uptake (internalization) and better reducing effect of mean immunofluorescence intensity of inflammatory proteins such as NF-κB and iNOS at in vitro RAW264.7 macrophage cell line. The radiographical study, ELISA test, RT-PCR study and H & E staining also indicated a reduction in joint tissue swelling, IL-6 and TNF-α levels diminution, fold change diminution in the mRNA expressions for NF-κB, IL-1β, IL-6 and PGE2 and maintenance of near normal histology at bone cartilage interface respectively. The results of metabolomic pathway analysis performed by LC-MS/MS method using the rat blood (plasma) collected from disease control and dual drug-loaded emulsions treatment groups revealed a new follow-up study to understand not only the disease progression but also the formulation therapeutic efficacy assessment.

Ebselen Optimized the Therapeutic Effects of Silver Nanoparticles for Periodontal Treatment.

Silver nanoparticles (AgNPs) possess excellent antibacterial effects on periodontal pathogens, but their clinical application is limited mainly due to their cytotoxicity through inducing oxidative stress in human cells. Ebselen disrupts the reactive oxygen species (ROS) scavenging in bacteria and relieves oxidative stress in mammalian cells. This study aimed to assess the antibacterial and anti-inflammatory effects of AgNPs and ebselen as well as the protective effect of ebselen, to further provide the theoretical basis for their future application in periodontal treatment. The antibacterial and anti-biofilm effects of the synthesized AgNPs combined with ebselen were assessed on Porphyromonas gingivalis (P. gingivalis), Streptococcus gordonii (S. gordonii), and Fusobacterium nucleatum (F. nucleatum) in planktonic condition and as biofilms. In addition, the intracellular bactericidal efficiency of AgNPs and ebselen was evaluated in P. gingivalis-infected human gingival fibroblasts (HGFs). The cytotoxicity, intracellular ROS levels, and potential antioxidative enzymes were detected in HGFs treated with AgNPs and ebselen. Further, the anti-inflammatory effects were evaluated by in vitro and in vivo experiments. The combination of AgNPs and ebselen showed excellent antibacterial effects against planktonic P. gingivalis and F. nucleatum and synergistic antibiofilm effects on all mono- and multi-species biofilms. In addition, ebselen significantly enhanced the intracellular bactericidal efficiency of AgNPs. Furthermore, ebselen combined with up to 20 μg/mL AgNPs showed no obvious cytotoxicity to HGFs. Evidently, ebselen alleviated the AgNPs-induced ROS by increasing the levels of glutathione and superoxide dismutase 2. Moreover, AgNPs and ebselen together declined the release of P. gingivalis-stimulated inflammatory cytokines both in vitro and in vivo, and reduced alveolar bone resorption effectively. AgNPs combined with ebselen would be an effective adjuvant for periodontal treatment owing to their synergistic antibacterial and anti-inflammatory effects.

Anti-inflammatory reprogramming of microglia cells by metabolic modulators to counteract neurodegeneration; a new role for Ranolazine

Microglia chronic activation is a hallmark of several neurodegenerative diseases, including the retinal ones, possibly contributing to their etiopathogenesis. However, some microglia sub-populations have anti-inflammatory and neuroprotective functions, thus making arduous deciphering the role of these cells in neurodegeneration. Since it has been proposed that functionally different microglia subsets also rely on different metabolic routes, we hypothesized that modulating microglia metabolism might be a tool to enhance their anti-inflammatory features. This would have a preventive and therapeutic potential in counteracting neurodegenerative diseases. For this purpose, we tested various molecules known to act on cell metabolism, and we revealed the anti-inflammatory effect of the FDA-approved piperazine derivative Ranolazine on microglia cells, while confirming the one of the flavonoids Quercetin and Naringenin, both in vitro and in vivo. We also demonstrated the synergistic anti-inflammatory effect of Quercetin and Idebenone, and the ability of Ranolazine, Quercetin and Naringenin to counteract the neurotoxic effect of LPS-activated microglia on 661W neuronal cells. Overall, these data suggest that using the selected molecules -also in combination therapies- might represent a valuable approach to reduce inflammation and neurodegeneration while avoiding long term side effects of corticosteroids.

Effect of minocycline, methyl prednisolone, or combination treatment on the colonic bacterial population in a state of colonic inflammation using the murine dextran sulfate sodium model

BackgroundSeveral reports demonstrated anti-inflammatory properties of minocycline in various inflammatory disorders including colitis. We have experimental evidence suggesting synergistic anti-inflammatory effect of minocycline with methyl prednisolone in reducing colitis severity in mice, but if this effect is in part related to modulating the composition of colonic microbiota is still unknown.Methodsthe effect of vehicle (V), minocycline (M), methyl prednisolone (MP), or combination (C) regimen on the composition of the microbiota of mice in a state of colon inflammation compared to untreated (UT) healthy mice was determined using 16s metagenomic sequencing, and the taxonomic and functional profiles were summarized.ResultsOverall, the bacterial flora from the phylum Firmicutes followed by Bacteroidota were found to be predominant in all the samples. However, the composition of Firmicutes was decreased relatively in all the treatment groups compared to UT group. A relatively higher percentage of Actinobacteriota was observed in the samples from the C group. At the genus level, Muribaculaceae, Bacteroides, Bifidobacterium, and Lactobacillus were found to be predominant in the samples treated with both drugs (C). Whereas “Lachnospiraceae NK4A136 group” and Helicobacter in the M group, and Helicobacter in the MP group were found to be predominant. But, in the UT group, Weissella and Staphylococcus were found to be predominant. Eubacterium siraeum group, Clostridia vadinBB60 group, Erysipelatoclostridium and Anaeroplasma genera were identified to have a significant (FDR p < 0.05) differential abundance in V compared to C and UT groups. While at the species level, the abundance of Helicobacter mastomyrinus, Massiliomicrobiota timonensis and uncultured Anaeroplasma were identified as significantly low in UT, C, and M compared to V group. Functional categories related to amino acid, carbohydrate, and energy metabolism, cell motility and cell cycle control were dominated overall across all the samples. Methane metabolism was identified as an enriched pathway. For the C group, “Colitis (decrease)” was among the significant (p = 1.81E-6) associations based on the host-intrinsic taxon set.ConclusionCombination regimen of minocycline plus methyl prednisolone produces a synergistic anti-inflammatory effect which is part related to alternation in the colonic microbiota composition.