Magnesium whitlockite nanoparticles: Hydrothermal synthesis, anti-inflammatory and anti-cancer potential.

This study revealed the potential of magnesium whitlockite [WH: Ca18Mg2(HPO4)2(PO4)12] nanoparticles (WH NPs) for anti-inflammatory and anti-cancer therapies. Although magnesium whitlockite possesses promising biological properties, its effects on inflammation and cancer remain unexplored. In this study, we address this gap by synthesizing WH NPs and demonstrating their multifaceted functionalities. Through detailed characterization, we revealed the synthesis pathway involving brushite as a precursor, with magnesium ions incorporated during hydrothermal treatment. WH NPs exhibited anti-inflammatory properties by significantly reducing the production of key inflammatory markers (NO, TNF-α, and IL-6). Furthermore, they display promising anti-cancer activity by inhibiting the proliferation of MDA-MB-231 breast cancer cells. Our findings not only establish a deeper understanding of WH NP synthesis but also highlight their potential for the development of innovative cancer and inflammatory treatments.

Chia nanoemulsion: anti-inflammatory mechanism, biological behavior and cellular interactions.

Aim: This study explores chia oil, rich in ω-3 fatty acids and nutraceutical components, as a potential remedy for diseases, especially those linked to inflammation and cancer. Methods/materials: A chia oil-based nanoemulsion, developed through single emulsification, underwent comprehensive analysis using various techniques. In vitro and in vivo assays, including macrophage polarization, nitrite and cytokine production, cellular uptake and biodistribution, were conducted to assess the anti-inflammatory efficacy. Results & conclusion: Results reveal that the chia nanoemulsion significantly inhibits inflammation, outperforming pure oil with twice the efficacy. Enhanced uptake by macrophage-like cells and substantial accumulation in key organs indicate its potential as an economical and effective anti-inflammatory nanodrug, addressing global economic and health impacts of inflammation-related diseases.

Nanoceria Anti-inflammatory and Antimicrobial Nanodrug: Cellular and Molecular Mechanism of Action.

INTRODUCTION: Nanoceria is a well-known nanomaterial with various properties, including antioxidant, proangiogenic, and therapeutic effects. Despite its potential, there are still aspects that require further exploration, particularly its anti-inflammatory and antimicrobial activities. METHOD: The global demand for novel anti-inflammatory and antimicrobial drugs underscores the significance of understanding nanoceria in both contexts. In this study, we evaluated the effect of nanoceria on macrophage polarization to better understand its anti-inflammatory effects. Additionally, we investigated the mechanism of action of nanoceria against Cryptococcus neoformans (ATCC 32045), Candida parapsilosis (ATCC 22019), Candida krusei (ATCC 6258), and Candida albicans. RESULT: The results demonstrated that nanoceria can polarize macrophages toward an anti-inflammatory profile, revealing the cellular mechanisms involved in the anti-inflammatory response. Concerning the antimicrobial effect, it was observed that nanoceria have a more pronounced impact on Candida parapsilosis, leading to the formation of pronounced pores on the surface of this species. CONCLUSION: Finally, biochemical analysis revealed transitory alterations, mainly in liver enzymes. The data support the use of nanoceria as a potential anti-inflammatory and antimicrobial drug and elucidate some of the mechanisms involved, shedding light on the properties of this nanodrug.

Methyl gallate nanomicelles impairs neutrophil accumulated in zymosan-induced arthritis.

Arthritis is a chronic disease that affects, approximately, 1 % of the total global population. It is characterized by chronic inflammation, accompanied in most of the cases of motor disability and sever pain. The main therapies available have high risk of failure and advanced treatments are scarce and highly cost. In this scenario, search for effective, safe and low-cost treatments is quite desirable. Methyl gallate (MG) is a plant-derived phenolic compound described to present remarkable anti-inflammatory effect in experimental models of arthritis. Thus, in this study we formulated nanomicelles of MG using Pluronic (F-127) as matrix and evaluated in vivo the pharmacokinetic, biodistribution and its effect in the mice model of zymosan-induced arthritis. The nanomicelles were formed with a size 126 nm. The biodistribution showed a ubiquitous tissue deposition with a renal excretion. The pharmacokinetics showed elimination half-life of 1.72 h and a clearance of 0.006 L/h. The oral pretreatment with nanomicelles containing MG (3.5 or 7 mg/kg) demonstrated a reduction in total leukocytes, neutrophils, and mononuclear cells from the inflammation site. The data supports the use of methyl gallate nanomicelles as an alternative drug for arthritis. DATA AVAILABILITY: All the data of this study are transparent.

Chitosan-graphene quantum dot based active film as smart wound dressing.

Graphene quantum dots (GQDs), are biocompatible materials, with mechanical strength and stability. Chitosan, has antibacterial and anti-inflammatory properties, and biocompatibility. Wound healing is a challenging process especially in chronic diseases and infection. In this study, films consisting of chitosan and graphene quantum dots were developed for application in infected wounds. The chitosan-graphene films were prepared in the acidic solution followed by slow solvent evaporation and drying. The chitosan-graphene films were characterized by the scanning electron microscopy, x-ray diffraction, atomic force microscopy, Raman spectroscopy and thermogravimetric analysis. The films' was evaluated by the wound healing assays, hemolytic potential, and nitrite production, cytokine production and swelling potential. The obtained films were flexible and well-structured, promoting cell migration, greater antibacterial activity, lower hemolytic activity, and maintaining wound moisture. Our data suggested that the use of graphene quantum dot-containing chitosan films would be an efficient and promising way in combating wounds.

Protective effect of methyl gallate on murine antigen-induced arthritis by inhibiting inflammatory process and bone erosion.

Methyl gallate (MG) is a plant-derived phenolic compound known to present remarkable anti-inflammatory effect in different experimental models, such as paw oedema, pleurisy, zymosan-induced arthritis and colitis. Herein we investigated the effect of MG in the mice model of antigen-induced arthritis (AIA), a model with complex inflammatory response, driven primally by immune process and that cause bone and cartilage erosion similarly found in rheumatoid arthritis. Arthritis was induced by intra-articular injection of albumin methylated from bovine serum (mBSA) in C57BL/6 male mice previously immunized. The dose-response analysis of MG (0.7-70 mg/kg; p.o) showed that maximum inhibition was reached with the dose of 7 mg/kg on paw oedema and cell infiltration induced by AIA at 7 h. Treatment with MG (7 mg/kg; p.o) or with the positive control, dexamethasone (Dexa, 10 mg/kg, ip) reduced AIA oedema formation, leukocyte infiltration, release of extracellular DNA and cytokine production 7 and 24 h (acute response). Mice treated daily with MG for 7 days showed no significant weight loss or liver and kidney toxicity contrary to dexamethasone that induced some degree of toxicity. Prolonged treatment with MG inhibited the late inflammatory response (28 days) reducing oedema formation, cell infiltration, synovial hyperplasia, pannus formation and cartilage degradation as observed in histopathological analyses. Ultimately, MG reduced bone resorption as evidenced by a decrease in tartrate-resistant acid phosphate (TRAP)-positive cells number in femur histology. Altogether, we demonstrate that MG ameliorates the inflammatory reaction driven primarily by the immune process, suggesting a potential therapeutic application in arthritis treatment.

Nanoparticle conjugated with aptamer anti-MUC1/Y for inflammatory arthritis.

Aptamers may form well-defined three-dimensional structures binding with high affinity and stability to a specific receptor. The aptamer anti-MUC1 isoform Y is one the most used due the affinity to MUC1, which is overexpressed in several types of cancer and inflammation process. In this study we have developed, characterized, in vitro as in vivo evaluated a nanoaptamer (anti-MUC1/Y) as a nanoagent for rheumatoid arthritis treatment. The results showed that a nanoaptamer with a size range of 241 nm was produced. The entrapment efficacy was 90% with a biodistribution showing a high hepatic uptake (>98%). The results in vivo showed a potent effect in arthritis experimental model, especially in low doses. The results corroborate the applicability of this nanosystem for RA treatment.

Intra-articular use of radium dichloride ([223Ra] RaCl2) showed relevant anti-inflammatory response on experimental arthritis model.

Rheumatoid arthritis (RA) is an inflammatory chronic autoimmune disease. The treatment of RA is difficult and, in many cases, ineffective, and the arsenal of drugs is limited. Due the longevity of the disease, RA may cause extreme musculoskeletal disorders with a high impact on quality of life. Also, RA is related with severe comorbidities decreasing the life expectancy. Finally, RA has been reported to impact in economy and healthy public. In this direction, the necessity to discover new strategies to efficiently treat RA is immediate. In this direction, we have reported the use of low doses of [223Ra] RaCl2 (radium dichloride) as intra-articular injection to treat RA. Mice were post-treated with [223Ra] RaCl2 (1.48 µCi; i.a.) 24 h after zymosan stimulus. Zymosan-induced arthrithis is responsible for leucocyte recruitment (total leukocytes, neutrophils, and mononuclear cells), which were inhibited by intra-articular injection of [223Ra] RaCl2 (69%, 77%, and 66%, respectively).

Rheumatoid arthritis treatment using hydroxychloroquine and methotrexate co-loaded nanomicelles: In vivo results.

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. It is a long-lasting autoimmune disease, which mainly affects the joints causing inflammation and swelling of the synovial joint. RA has a significant impact on the ability to perform daily activities including simple work and household chores. Nonetheless, due to the long periods of pain and the continuous use of anti-inflammatory drugs, RA can debilitate the quality of life and increases mortality. Current therapeutic approaches to treat RA aim to achieve prolonged activity and early and persistent remission of the disease, with the gradual adoption of different drugs available. In this study, we developed a novel hydroxychloroquine and methotrexate co-loaded Pluronic® F-127 nanomicelle and evaluated its therapeutic effects against RA. Our results showed that drug-loaded nanomicelles were capable of modulating the inflammatory process of RA and reducing osteoclastogenesis, edema, and cell migration to the joint. Overall, compared to the free drugs, the drug-loaded nanomicelles showed a 2-fold higher therapeutic effect.

Methyl gallate attenuates inflammation induced by Toll-like receptor ligands by inhibiting MAPK and NF-Κb signaling pathways.

OBJECTIVE AND DESIGN: Methyl gallate (MG) is a prevalent polyphenol in the plant kingdom, which may be related to the effects of several medicinal plants. Although it is widely reported that polyphenols have therapeutic effects, there are few studies demonstrating that MG has anti-inflammatory action. This study aimed to investigate the molecular mechanism behind the anti-inflammatory activity of MG and its effect on hyperalgesia. METHODS: Swiss mice were pretreated orally with different doses of MG and subjected to i.pl. injection of zymosan to induce paw edema. RAW264.7 macrophages and BMDMs stimulated with different TLR agonists such as zymosan, LPS, or Pam3CSK4 were used to investigate the molecular mechanisms of MG RESULTS: MG inhibits zymosan-induced paw edema and hyperalgesia and modulates molecular pathways crucial for inflammation development. Pretreatment with MG inhibited cytokines production and NF-κB activity by RAW 264.7 cells stimulated with zymosan, Pam3CSK4 or LPS, but not with PMA. Moreover, pretreatment with MG decreased IκB degradation, nuclear translocation of NF-κBp65, c-jun and c-fos and ERK1/2, p38 and JNK phosphorylation. CONCLUSION: Thus, the results of this study demonstrate that MG has a promising anti-inflammatory effect and suggests an explanation of its mechanism of action through the inhibition of NF-κB signaling and the MAPK pathway.

The cannabinoid 2 receptor agonist ß-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration.

OBJECTIVE AND DESIGN: ß-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB2) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB2 agonist, GP1a in inflammatory experimental model induced by Mycobacterium bovis (BCG). METHODS: C57Bl/6 mice were pretreated orally with BCP (0.5-50 mg/kg) or intraperitonealy with GP1a (10 mg/kg) 1 h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB2 agonists on neutrophils function was evaluated in vitro. RESULTS: ß-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-α and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B4 (LTB4), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 µM) impaired chemotaxis toward LTB4 and adhesion to endothelial cells stimulated with TNF-α, and both, BCP and GP1a, impaired LTB4-induced actin polymerization. CONCLUSION: These results suggest that the CB2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.

Anti-inflammatory Effect of Methyl Gallate on Experimental Arthritis: Inhibition of Neutrophil Recruitment, Production of Inflammatory Mediators, and Activation of Macrophages.

Methyl gallate (MG) is a prevalent phenolic acid in the plant kingdom, and its presence in herbal medicines might be related to its remarkable biological effects, such as its antioxidant, antitumor, and antimicrobial activities. Although some indirect evidence suggests anti-inflammatory activity for MG, there are no studies demonstrating this effect in animal models. Herein, we demonstrated that MG (0.7-70 mg/kg) inhibited zymosan-induced experimental arthritis in a dose-dependent manner. The oral administration of MG (7 mg/kg) attenuates arthritis induced by zymosan, affecting edema formation, leukocyte migration, and the production of inflammatory mediators (IL-1ß, IL-6, TNF-α, CXCL-1, LTB4, and PGE2). Pretreatment with MG inhibited in vitro neutrophil chemotaxis elicited by CXCL-1, as well as the adhesion of these cells to TNF-α-primed endothelial cells. MG also impaired zymosan-stimulated macrophages by inhibiting IL-6 and NO production, COX-2 and iNOS expression, and intracellular calcium mobilization. Thus, MG is likely to present an anti-inflammatory effect by targeting multiple cellular events such as the production of various inflammatory mediators, as well as leukocyte activation and migration.

Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolius is a species of plant from the Anacardiaceae family, which can be found in different regions of Brazil. Schinus is popularly known as aroeirinha, aroeira-vermelha, or Brazilian pepper. In folk medicine, S. terebinthifolius is used for several disorders, including inflammatory conditions, skin wounds, mucosal membrane ulcers, respiratory problems, gout, tumors, diarrhea and arthritis. According to chemical analyses, gallic acid, methyl gallate and pentagalloylglucose are the main components of hydroalcoholic extracts from S. terebinthifolius leaves. In the present study, we demonstrated the ability of a hydroalcoholic extract to inhibit cell migration in arthritis and investigated the mechanisms underlying this phenomenon. MATERIALS AND METHODS: The anti-inflammatory effect of S. terebinthifolius hydroalcoholic leaf extract (ST-70) was investigated in a zymosan-induced experimental model of inflammation. Male Swiss and C57Bl/6 mice received zymosan (100 µg/cavity) via intra-thoracic (i.t.) or intra-articular (i.a.) injection after oral pre-treatment with ST-70. The direct action of ST-70 on neutrophils was evaluated via chemotaxis. RESULTS: ST-70 exhibited a dose-dependent effect in the pleurisy model. The median effective dose (ED50) was 100mg/kg, which inhibited 70% of neutrophil accumulation when compared with the control group. ST-70 reduced joint diameter and neutrophil influx for synovial tissues at 6h and 24h in zymosan-induced arthritis. Additionally, ST-70 inhibited synovial interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (CXCL1/KC) and Tumor Necrosis Factor (TNF)-α production at 6h and CXCL1/KC and IL-1ß production at 24h. The direct activity of ST-70 on neutrophils was observed via the impairment of CXCL1/KC-induced chemotaxis in neutrophils. Oral administration of ST-70 did not induce gastric damage. Daily administration for twenty days did not kill any animals. In contrast, similar administrations of diclofenac induced gastric damage and killed all animals by the fifth day. CONCLUSIONS: Our results demonstrated significant anti-inflammatory effects of ST-70, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, such as joint inflammation.