Synergistic Anti-inflammatory Effect Research Articles

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.

Curcumin-incorporated EGCG-based nano-antioxidants alleviate colon and kidney inflammation via antioxidant and anti-inflammatory therapy.

Natural remedies are gaining attention as promising approaches to alleviating inflammation, yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects. To overcome these limitations, we have developed a novel nano-antioxidant (EK) based on epigallocatechin gallate (EGCG) aimed at enhancing the oral and systemic bioavailability, as well as the anti-inflammatory efficacy, of curcumin (Cur) in conditions such as acute colon and kidney inflammation. EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine (K), resulting in the formation of EGCG oligomers. These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm. In vitro studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages, a key component in the body's inflammatory response. By efficiently encapsulating curcumin within these EK nanoparticles, we create Cur@EK, a formulation that demonstrates a synergistic anti-inflammatory effect. Specifically, Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-α and IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages, highlighting its potent anti-inflammatory properties. When administered either orally or intravenously, Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury. These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact, offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.

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.

Enhancing the bioavailability of quercetin via the construction of carboxymethylated curdlan/quercetin nanocomplex

Quercetin, renowned for its antioxidant and anti-inflammatory properties, holds promise for promoting human health. However, its limited solubility and stability hinders the bioactive efficacy. This study aims to enhance the bioavailability of quercetin by developing a carboxymethylated curdlan and quercetin complex (CM-Cur/QT) through an anti-solvent dialysis strategy. The CM-Cur/QT complex exhibited a spherical structure with a diameter approximately 300 nm, demonstrating improved solubility and stability. Non-covalent interaction involving the C-7 OH, C-3 OH, C-4′ OH, and C-3′OH in quercetin (QT) and the COOH group of carboxymethylated curdlan (CM-Cur) were found to contribute to the formation of CM-Cur/QT complex. During in vitro digestion, the CM-Cur/QT complex showed enhanced bio-accessibility of QT and increased antioxidant efficacy. Additionally, the CM-Cur/QT complex facilitated internalization of QT in macrophages and exerted a potential synergistic anti-inflammatory effect, which was characterized by the inhibition of intracellular reactive oxygen species (ROS) generation and a reduction in inflammatory secretion in M1 phenotype macrophage. These findings highlight the ability of the quercetin-loaded β-glucan complex (CM-Cur/QT) to enhance the original bioactivities of QT, particularly in modulating macrophage function.

Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation

Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the “vector” of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases.

Synergistic approach for acne vulgaris treatment using glycerosomes loaded with lincomycin and lauric acid: Formulation, in silico, in vitro, LC-MS/MS skin deposition assay and in vivo evaluation

This study aims to develop a pharmaceutical formulation that combines the potent antibacterial effect of lincomycin and lauric acid against Cutibacterium acnes (C. acnes), a bacterium implicated in acne. The selection of lauric acid was based on an in silico study, which suggested that its interaction with specific protein targets of C. acnes may contribute to its synergistic antibacterial and anti-inflammatory effects. To achieve our aim, glycerosomes were fabricated with the incorporation of lauric acid as a main constituent of glycerosomes vesicular membrane along with cholesterol and phospholipon 90H, while lincomycin was entrapped within the aqueous cavities. Glycerol is expected to enhance the cutaneous absorption of the active moieties via hydrating the skin. Optimization of lincomycin-loaded glycerosomes (LM-GSs) was conducted using a mixed factorial experimental design. The optimized formulation; LM-GS4 composed of equal ratios of cholesterol:phospholipon90H:Lauric acid, demonstrated a size of 490 ± 17.5 nm, entrapment efficiency-values of 90 ± 1.4 % for lincomycin, and97 ± 0.2 % for lauric acid, and a surface charge of −30.2 ± 0.5mV. To facilitate its application on the skin, the optimized formulation was incorporated into a carbopol hydrogel. The formed hydrogel exhibited a pH value of 5.95 ± 0.03 characteristic of pH-balanced skincare and a shear-thinning non-Newtonian pseudoplastic flow. Skin deposition of lincomycin was assessed using an in-house developed and validated LC-MS/MS method employing gradient elution and electrospray ionization detection. Results revealed that LM-GS4 hydrogel exhibited a two-fold increase in skin deposition of lincomycin compared to lincomycin hydrogel, indicating improved skin penetration and sustained release. The synergistic healing effect of LM-GS4 was evidenced by a reduction in inflammation, bacterial load, and improved histopathological changes in an acne mouse model. In conclusion, the proposed formulation demonstrated promising potential as a topical treatment for acne. It effectively enhanced the cutaneous absorption of lincomycin, exhibited favorable physical properties, and synergistic antibacterial and healing effects. This study provides valuable insights for the development of an effective therapeutic approach for acne management.

In Vitro Synergistic Antibacterial and Anti-Inflammatory Effects of Nisin and Lactic Acid in Yogurt against Helicobacter pylori and Human Gastric Cells.

Helicobacter pylori is a bacterium that naturally thrives in acidic environments and has the potential to induce various gastrointestinal disorders in humans. The antibiotic therapy utilized for treating H. pylori can lead to undesired side effects, such as dysbiosis in the gut microbiota. The objective of our study was to explore the potential antibacterial effects of nisin and lactic acid (LA) in yogurt against H. pylori. Additionally, we investigated the anti-inflammatory effects of nisin and LA in human gastric (AGS) cells infected with H. pylori. Nisin and LA combination showed the strongest inhibitory activity, with confirmed synergy at 0.375 fractional inhibitory concentration index. Also, post-fermented yogurt with incorporation of nisin exhibited antibacterial effect against H. pylori. The combination of nisin and LA resulted in a significant reduction of mRNA levels of bacterial toxins of H. pylori and pro-inflammatory cytokines in AGS cells infected with H. pylori. Furthermore, this also increased bacterial membrane damage, which led to DNA and protein leakage in H. pylori. Overall, the combination of nisin and LA shows promise as an alternative therapy for H. pylori infection. Additionally, the incorporation of nisin into foods containing LA presents a potential application. Further studies, including animal research, are needed to validate these findings and explore clinical applications.

Synergistic and Long-Lasting Wound Dressings Promote Multidrug-Resistant Staphylococcus Aureus-Infected Wound Healing.

Multidrug-resistant staphylococcus aureus infected wounds can lead to nonhealing, systemic infections, and even death. Although advanced dressings are effective in protecting, disinfecting, and maintaining moist microenvironments, they often have limitations such as single functionality, inadequate drug release, poor biosafety, or high rates of drug resistance. Here, a novel wound dressing comprising glycyrrhizic acid (GA) and tryptophan-sorbitol carbon quantum dots (WS-CQDs) was developed, which exhibit synergistic and long-lasting antibacterial and anti-inflammatory effects. We investigated the characterization, mechanical properties, synergistic antibacterial effects, sustained-release properties, and cytotoxicity of GA/WS-CQDs hydrogels in vitro. Additionally, we performed transcriptome sequence analysis to elucidate the antibacterial mechanism. Furthermore, we evaluated the biosafety, anti-inflammatory effects, and wound healing ability of GA/WS-CQDs dressings using an in vivo mouse model of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds. The prepared GA/WS-CQDs hydrogels demonstrated superior anti-MRSA effects compared to common antibiotics in vitro. Furthermore, the sustained release of WS-CQDs from GA/WS-CQDs hydrogels lasted for up to 60 h, with a cumulative release of exceeding 90%. The sustained-released WS-CQDs exhibited excellent anti-MRSA effects, with low drug resistance attributed to DNA damage and inhibition of bacterial biofilm formation. Notably, in vivo experiments showed that GA/WS-CQDs dressings reduced the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and significantly promoted the healing of MRSA-infected wounds with almost no systemic toxicity. Importantly, the dressings did not require replacement during the treatment process. These findings emphasize the high suitability of GA/WS-CQDs dressings for MRSA-infected wound healing and their potential for clinical translation.