Iron chelating, antioxidant, and anti-inflammatory properties of brazilin from Caesalpinia sappan Linn.

Background: Iron overload and inflammation are severe conditions that can lead to various chronic diseases. However, the current iron chelator drugs have their limitations. The phytochemical compounds from herbals, such as brazilin, the major active compound in Caesalpinia sappan Linn., have significant therapeutic potential in various chronic diseases. Our study was designed to examine the effect of brazilin on iron chelating properties, antioxidant activity in hepatocytes, and anti-inflammatory potential in macrophages. Methods: This study focused on the isolation, purification, and evaluation of brazilin, the principal bioactive constituent found in C. sappan wood. Brazilin was extracted via methanol maceration followed by column chromatography purification. The purified compound was characterized using high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). The antioxidant potential of brazilin was assessed by in vitro assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazolin-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). Furthermore, its cellular antioxidant activity was evaluated using hydrogen peroxide-induced oxidative stress in the hepatocellular carcinoma cell line (Huh-7). The iron-chelating capacity of brazilin was determined spectrophotometrically, and Job's plot method was used to elucidated the stoichiometry of the iron-brazilin complex formation. The anti-inflammatory properties of brazilin were investigated in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7). Nitric oxide (NO) inhibition was quantified using the Griess reagent, while the expression levels of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were evaluated by RT-qPCR. Results: The results demonstrated that brazilin exhibited potent antioxidant activity in vitro and hepatocytes in a concentration-dependent manner. It also showed anti-inflammatory activity, in which NO production was significantly reduced and IL-6 and TNF-α expression in LPS-induced macrophages were repressed. Furthermore, it can bind ferric and ferrous ions. Brazilin acts as a bidentate iron chelator that forms a complex with iron in a 2:1 ratio, and two water molecules are used as additional chelators in this complex. Conclusions: Our findings have significant implications. Brazilin can potentially alleviate the harmful effects of iron-induced oxidative stress and inflammatory disorders.

Potential of plant-based polysaccharides as therapeutic agents in ulcerogenic diseases of the gastrointestinal tract: A review.

In recent years, natural polysaccharides (PSs) have attracted increasing interest because of their remarkable biological properties and potential in various areas, such as medicine, and food. This study aimed to present a detailed review of the evidence on the therapeutic potential of PSs for the treatment of gastrointestinal diseases. The main evidence was correlated with their chemical composition, mechanism of action and therapeutic effect. The main results showed that the action can be attributed to their ability to suppress excessive inflammatory responses, regulating the expression of cytokines and interleukins, reducing intestinal inflammation and promoting wound healing. Furthermore, we discussed how PSs help in the repair of the intestinal mucosa and related these effects with the composition of monosaccharides. A detailed analysis was performed on the ability of PSs to modulate the intestinal microbiota, promoting the growth of beneficial bacteria and suppressing inflammatory bacteria, in addition to its probiotic action with production of short-chain fatty acids. All this evidence was also taken into a broader context, in which the main challenges in processing PSs were considered and strategies to circumvent them were pointed out. Therefore, this review sought to demonstrate the great potential and viability of PSs as innovative and effective therapeutic agents.

Antinociceptive, anti-inflammatory, and antioxidant effects of a flavonoid-rich phytocomplex from the leaves of Celtis iguanaea (jacq.) Sargent (Cannabaceae).

We demonstrated the antinociceptive and anti-inflammatory effects of the ethyl acetate leaf extract of Celtis iguanaea (Jacq.) Sargent (EAECi) in mice. The in vitro antioxidant activity of EAECi and its phytoconstituents was also investigated. The antinociceptive effect of EAECi is attributed to its anti-inflammatory activity, as evidenced by its anti-hyperalgesic and antiedematogenic effects. EAECi reduced polymorphonuclear cell migration, myeloperoxidase activity, pro-inflammatory cytokines (TNF-α and IL-1ß), and PGE2 levels. The levels of anti-inflammatory cytokines (IL-4 and IL-10) were increased compared to the vehicle-treated groups. The overall antioxidant capacity of EAECi is noteworthy, with the Electrochemical Index determined by Differential Pulse Voltammetry being 42.7 µA/V. Concurrently, Square Wave Voltammetry revealed the reversibility of the redox process (Ep1a/Ep1c) at 0.254 V. The presence of twenty-six phytochemicals, primarily flavone aglycones, was suggested by paper-spray mass spectrometry. These findings represent a step towards validating C. iguanaea leaf extract for treating acute inflammatory conditions.

An In-depth Review on Argemone mexicana in the Management of Liver Health and Liver Cancer.

INTRODUCTION: Argemone mexicana, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of Argemone mexicana in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of Argemone mexicana. METHODOLOGY: A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of Argemone mexicana, specifically emphasizing its impact on liver health and cancer. RESULTS: The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of Argemone mexicana, further well-designed trials are warranted to establish its clinical efficacy. CONCLUSION: In conclusion, Argemone mexicana shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of Argemone mexicana in liver health and cancer management.

Yogurt enriched with nanoencapsulated anthocyanins: Effects on the modulation of the gut microbiota and its infuence on health.

Anthocyanins are phenolic compounds present in various plant products with interesting functional characteristics studied by science, such as their anti-inflammatory and antioxidant activities, among others. However, anthocyanins are considered unstable to various factors, which can affect their functional capacity. For this reason, some technologies, such as nanoencapsulation, are being applied to ensure their functional capacity effectively. The incorporation of anthocyanins in yogurt has shown various benefits, such as the ability to inhibit pathogenic microorganisms, reduce enzyme activity, and prolong the shelf life of the product. Additionally, the functional effects include their ability to modulate the gut microbiota, generating antioxidant, anti-inflammatory, and even antiproliferative responses, thereby reducing the capacity of tumor progression. For these reasons, this graphic review discussed the functional effects of yogurt enriched with nanoencapsulated anthocyanins on the gut microbiota and its influence on human health.

Association of COX-inhibitors with cancer patients' survival under chemotherapy and radiotherapy regimens: a real-world data retrospective cohort analysis.

Introduction: We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy. Methods: The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period. Results: Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits' risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes. Discussion: Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

Structure and Intercalation of Cysteine-Asparagine-Serine Peptide into Montmorillonite as an Anti-Inflammatory Agent Preparation-A DFT Study.

Peptides are receiving significant attention in pharmaceutical sciences due to their applications as anti-inflammatory drugs; however, many aspects of their interactions and mechanisms at the molecular level are not well-known. This work explores the molecular structure of two peptides-(i) cysteine (Cys)-asparagine (Asn)-serine (Ser) (CNS) as a molecule in the gas phase and solvated in water in zwitterion form, and (ii) the crystal structure of the dipeptide serine-asparagine (SN), a reliable peptide indication whose experimental cell parameters are well known. A search was performed by means of atomistic calculations based on density functional theory (DFT). These calculations matched the experimental crystal structure of SN, validating the CNS results and useful for assignments of our experimental spectroscopic IR bands. Our calculations also explore the intercalation of CNS into the interlayer space of montmorillonite (MNT). Our quantum mechanical calculations show that the conformations of these peptides change significantly during intercalation into the confined interlayer space of MNT. This intercalation is energetically favorable, indicating that this process can be a useful preparation for therapeutic anti-inflammatory applications and showing high stability and controlled release processes.

In Vitro Antioxidant, Anti-Inflammatory Activity and Bioaccessibility of Ethanolic Extracts from Mexican Moringa oleifera Leaf.

This study aimed to assess the antioxidant and anti-inflammatory properties, and bioaccessibility of Moringa oleifera ethanolic extracts using pressurized liquid extraction with varying ethanol concentrations (0%, 30%, 50%, 70%, and 100%) in water-ethanol mixtures. Quercetin derivatives and neochlorogenic acid were identified as major compounds via high-performance liquid chromatography with diode array detection. The 70% ethanol extract displayed the highest antioxidant activity and phenolic content, highlighting a strong correlation between phenolics and antioxidant potential. Extracts prepared with 50% and 70% ethanol (30 µg/mL) significantly inhibited TNF-α, IL-1ß, and IL-6 cytokine secretion, with the 70% ethanol extract demonstrating robust anti-inflammatory effects. During in vitro digestion (oral, gastric, and intestinal phases), minimal changes were noted in most phenolic compounds' post-oral phase, but reductions occurred after the gastric phase. Substantial decreases in major compounds and antioxidant activity were observed in post-gastric and intestinal phases. Overall, ethanolic extracts of Moringa oleifera, particularly those with 70% ethanol, exhibit promising antioxidant and anti-inflammatory properties, suggesting potential for developing therapeutic agents against oxidative stress and inflammation-related disorders. However, it is essential to protect these compounds to prevent their degradation during digestion.

10-Gingerol Increases Antioxidant Enzymes and Attenuates Lipopolysaccharide-Induced Inflammation by Modulating Adipokines in 3T3-L1 Adipocytes.

BACKGROUND: Obesity increases reactive oxygen species production and alters adipokines levels, resulting in a low-grade chronic inflammation state, which contributes to tissue metabolic dysfunction. 10-gingerol, a phenol present in ginger, has shown potential anti-obesogenic effects in vitro. However, the antioxidant and anti-inflammatory properties of 10-gingerol have not been approached. The aim of this study was to investigate the effects of 10-gingerol on antioxidant enzymes' expression and adipokine production in 3T3-L1 adipocytes in response to lipopolysaccharide (LPS)-induced inflammation. METHODS: 10-gingerol antioxidant capacity was assessed through Oxygen Radical Absorbance Capacity (ORAC) , Ferric Reducing Antioxidant Power (FRAP), and radical scavenging activity of 2,2-diphenyl-2-picrylhydrazyl (DPPH) assays. 3T3-L1 cells were differentiated and stimulated with 100 ng/mL LPSs. Then, 15 µg/mL 10-gingerol was added for 48 h. The mRNA expression and protein abundance of antioxidant enzymes were evaluated by qPCR and Western blot, respectively. Adipokine levels were determined by ELISA. RESULTS: 10-gingerol showed low FRAP and DPPH values but a moderate ORAC value. Moreover, 10-gingerol increased Gpx1 and Sod1 but downregulated Cat expression. Additionally, 10-gingerol significantly increased CAT and GPx1 levels but not SOD-1. Finally, adiponectin and leptin concentrations were increased while resistin and tumor necrosis factor alpha (TNFα) were decreased by 10-gingerol. CONCLUSIONS: 10-gingerol presented antioxidant potential by increasing antioxidant enzymes and attenuated LPS-induced inflammation by modulating adipokines in 3T3-L1 adipocytes.

Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation.

Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

Antidiabetic and Anti-Inflammatory Effect of Cinnamomum cassia Oil in Alloxan-Induced Diabetic Rats.

Diabetes mellitus presents a great diversity of treatments that cause adverse effects; therefore, plants are a source of compounds that may have fewer adverse effects; Cinnamomum cassia (C. cassia) has compounds with potential antidiabetic activity. The objective was to evaluate the antidiabetic effect of C. cassia oil (CCO) and its impact on oxidative stress in Wistar rats. Five groups were evaluated: (1) sham (SH), (2) 300 mg/kg CCO (CCO), (3) diabetic (D) induced with alloxan, (4) D + 300 mg/kg of CCO (D + CCO), and (5) D + 500 mg/kg of metformin (D + MET); all were treated for 5 days. CCO did not show alteration in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) vs. SH. D + CCO vs. D significantly reduced glucose (333 ± 109 vs. 458 ± 81 mg/dL), ALT (66 ± 15 vs. 160 ± 54 U/L), AST (119 ± 26 vs. 243 ± 104 U/L), and blood urea nitrogen (18.8 ± 2.3 vs. 29.2 ± 6.9 mg/dL). No significant changes were observed in D + CCO vs. D in malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD), whereas a significant reduction in MDA and GSH was achieved in D + MET, with an increase in SOD. There was a reduction in Rela and Gpx in D + CCO and D + MET vs. D. CCO has antidiabetic and anti-inflammatory effects and reduces ALT, AST, and BUN levels.

A Patent-Pending Ointment Containing Extracts of Five Different Plants Showed Antinociceptive and Anti-Inflammatory Mechanisms in Preclinical Studies.

Background/Objectives: The antinociceptive and anti-inflammatory effects of a patent-pending ointment containing plant extracts from Eucalyptus globulus, Curcuma longa, Hamamelis virginiana, Echinacea purpurea, and Zingiber officinale were evaluated. Methods: Plant extracts were chemically characterized by gas chromatography-mass spectroscopy. The antinociceptive activity of the ointment was assessed using the hot plate, tail flick, and formalin tests, whereas the anti-inflammatory activity was measured using the acute and chronic TPA-induced ear edema tests. Mechanisms of action were evaluated using inhibitors from signaling pathways related to pain response and by using histological analysis and assessing the expression and activity of pro-inflammatory mediators. Results: The ointment showed antinociceptive and anti-inflammatory effects like those observed with diclofenac gel (1.16% v/v) and ketoprofen gel (2.5% v/v). The antinociceptive actions of the ointment are mediated by the possible participation of the opiodergic system and the nitric oxide pathway. The anti-inflammatory response was characterized by a decrease in myeloperoxidase (MPO) activity and by a reduction in ear swelling and monocyte infiltration in the acute inflammation model. In the chronic model, the mechanism of action relied on a decrease in pro-inflammatory mediators such as COX-2, IL-1ß, TNF-α, and MPO. An in-silico study with myristic acid, one of the compounds identified in the ointment's plant mixture, corroborated the in vivo results. Conclusions: The ointment showed antinociceptive activities mediated by the decrease in COX-2 and NO levels, and anti-inflammatory activity due to the reduction in IL-1ß and TNFα levels, a reduction in MPO activity, and a decrease in NF-κB and COX-2 expression.

Bioactive properties of spearmint, orange peel, and baby sage oleoresins obtained by supercritical CO2 extraction and their integration into dark chocolate.

This study investigated the potential health benefits of spearmint, orange peel, and baby sage oleoresins extracted using supercritical CO2 and subsequently emulsified. The oleoresins were incorporated into dark chocolate, and their impact on physicochemical properties was evaluated. Characterization revealed rich sources of phenolic compounds, carotenoids, and volatile compounds in these oleoresins. In vitro studies demonstrated anti-obesogenic, antioxidant, anti-inflammatory, and neuroprotective properties of the emulsified oleoresins. However, only physicochemical properties were determined for the formulations of dark chocolate with these emulsified oleoresins. Chocolate formulations fortified with these emulsions displayed a softer texture, lower water activity, and solid-like behavior. The findings suggest that these oleoresins could serve as nutraceutical agents for mitigating metabolic syndrome and associated pathologies. Incorporating them into chocolate matrices offers a practical approach to formulating functional foods. Further research is warranted to explore the preventive and therapeutic efficacy in an in vivo model.

How to enhance MSCs therapeutic properties? An insight on potentiation methods.

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising tool in the field of regenerative medicine due to their unique therapeutic properties as they can differentiate into multiple cell types and exert paracrine effects. However, despite encouraging results obtained in preclinical studies, clinical trials have not achieved the same levels of efficacy. To improve the therapeutic properties of MSCs, several strategies have been explored. Therefore, in this review, the therapeutic properties of MSCs will be analyzed, and an update and overview of the most prominent approaches used to enhance their therapeutic capabilities will be provided. These approaches include using drugs, molecules, strategies based on biomaterials, and modification parameters in culture. The strategy described shows several common factors among those affected by these strategies that lead to an enhancement of the MSCs therapeutic properties such as the activation of the PI3K/AKT pathway and the increased expression of Heat Shock Proteins and Hypoxia-Inducible Factor. The combined effect of these elements shift MSCs towards a glycolytic state, suggesting this shift is essential for their enhancement.

Chronic post-ischemic pain (CPIP) a model of complex regional pain syndrome (CRPS-I): Role of oxidative stress and inflammation.

Complex regional pain syndrome (CRPS) presents as a persistent and distressing pain condition often stemming from limb trauma or ischemia, manifesting as either CRPS-I (without initial nerve injury) or CRPS-II (accompanied by nerve injury). Despite its prevalence and significant impact on functionality and emotional well-being, standard treatments for CRPS remain elusive. The multifaceted nature of CRPS complicates the identification of its underlying mechanisms. In efforts to elucidate these mechanisms, researchers have turned to animal models such as chronic post-ischemic pain (CPIP), which mirrors the symptoms of CRPS-I. Various mechanisms have been proposed to underlie the acute and chronic pain experienced in CRPS-I, including oxidative stress and inflammation. Traditional treatment approaches often involve antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids. However, these methods frequently fall short of providing adequate relief. Accordingly, there is a growing interest in exploring alternative treatments, such as antioxidant supplementation, anti-inflammatory agents, and non-pharmacological interventions. Future research directions should focus on optimizing treatment strategies and addressing remaining gaps in knowledge to improve patient outcomes. This review aims to delve into the pathophysiological mechanisms implicated in the CPIP model, specifically focusing on oxidative stress and inflammation, with the ultimate goal of proposing innovative therapeutic strategies for alleviating the symptoms of CRPS-I.

Optimization of Phenolic Compounds Extraction from Aerial Parts of Fabiana punensis S. C. Arroyo by Ultrasound- and Microwave-Assisted Extraction.

Fabiana punensis S. C. Arroyo is a subshrub or shrub that is indigenous to the arid and semiarid region of northern Argentina and is known to possess several medicinal properties. The objective of this study was to optimize the extraction conditions so as to maximize the yield of bioactive total phenolic compound (TPC) and flavonoids (F) of F. punensis' aerial parts by using non-conventional extraction methods, namely ultrasound-assisted extraction, UAE, and microwave-assisted extraction, MAE, and to compare the biological activities and toxicity of optimized extracts vs. conventional extracts, i.e., those gained by maceration. Response Surface Methodology (RSM) was used to apply factorial designs to optimize the parameters of extraction: solid-to-liquid ratio, extraction time, ultrasound amplitude, and microwave power. The experimental values for TPC and F and antioxidant activity under the optimal extraction conditions were not significantly different from the predicted values, demonstrating the accuracy of the mathematical models. Similar HPLC-DAD patterns were found between conventional and UAE- and MAE-optimized extracts. The main constituents of the extracts correspond to phenolic compounds (flavonoids and phenolic acids) and apigenin was identified. All extracts showed high scavenger capacity on ABTS•+, O2•- and H2O2, enabling the inhibition of the pro-inflammatory enzymes xanthine oxidase (XO) and lipoxygenase (LOX). They also showed an antimutagenic effect in Salmonella Typhimurium assay and cytotoxic/anti-proliferative activity on human melanoma cells (SKMEL-28). Toxicological evaluation indicates its safety. The results of this work are important in the development of efficient and sustainable methods for obtaining bioactive compounds from F. punensis for the prevention of chronic degenerative diseases associated with oxidative stress, inflammation, and DNA damage.

Inflammatory turmoil within: an exploration of autoinflammatory disease genetic underpinnings, clinical presentations, and therapeutic approaches.

Systemic autoinflammatory diseases (SAIDs) arise from dysregulated innate immune system activity, which leads to systemic inflammation. These disorders, encompassing a diverse array of genetic defects classified as inborn errors of immunity, are significant diagnostic challenges due to their genetic heterogeneity and varied clinical presentations. Although recent advances in genetic sequencing have facilitated pathogenic gene discovery, approximately 40% of SAIDs patients lack molecular diagnoses. SAIDs have distinct clinical phenotypes, and targeted therapeutic approaches are needed. This review aims to underscore the complexity and clinical significance of SAIDs, focusing on prototypical disorders grouped according to their pathophysiology as follows: (i) inflammasomopathies, characterized by excessive activation of inflammasomes, which induces notable IL-1ß release; (ii) relopathies, which are monogenic disorders characterized by dysregulation within the NF-κB signaling pathway; (iii) IL-18/IL-36 signaling pathway defect-induced SAIDs, autoinflammatory conditions defined by a dysregulated balance of IL-18/IL-36 cytokine signaling, leading to uncontrolled inflammation and tissue damage, mainly in the skin; (iv) type I interferonopathies, a diverse group of disorders characterized by uncontrolled production of type I interferons (IFNs), notably interferon α, ß, and ε; (v) anti-inflammatory signaling pathway impairment-induced SAIDs, a spectrum of conditions characterized by IL-10 and TGFß anti-inflammatory pathway disruption; and (vi) miscellaneous and polygenic SAIDs. The latter group includes VEXAS syndrome, chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis, Schnitzler syndrome, and Still's disease, among others, illustrating the heterogeneity of SAIDs and the difficulty in creating a comprehensive classification. Therapeutic strategies involving targeted agents, such as JAK inhibitors, IL-1 blockers, and TNF inhibitors, are tailored to the specific disease phenotypes.

Exploring the Therapeutic Potential of Green-Synthesized Gold Nanoparticles and Ericaria selaginoides Extract for Inflammatory Bowel Disease.

Addressing disease remission and treatment adherence in inflammatory bowel diseases (IBDs), such as Crohn's disease, poses significant challenges due to underlying oxidative and inflammatory processes. Nanotechnology emerges as a promising avenue for enhancing therapeutic outcomes in IBD by optimizing drug bioactivity, reducing toxicity, and extending circulation time. Gold nanoparticles, known for their resistance to gastrointestinal pH and possessing antioxidant and anti-inflammatory properties, offer particular promise. They can be produced by green synthesis with seaweed Ericaria selaginoides (ES), itself associated with gastroprotective and anti-inflammatory activities. In a murine model of Crohn's disease induced with 8% acetic acid, pretreatment with dexamethasone (0.2 mL/30 g) or Au@ES (25 and 50 mg/kg) effectively mitigated inflammatory features. Notably, ES (50 mg/kg) and Au@ES (50 mg/kg) administration resulted in significant reductions in both macroscopic and microscopic inflammation scores compared to the disease control group. Furthermore, these treatments normalized inflammatory cytokine expression while safeguarding myenteric plexus glial cells. They also impeded neutrophil activation, leading to reduced myeloperoxidase activity and lipid peroxidation, coupled with increased glutathione levels. In conclusion, ES and Au@ES exhibit potent efficacy in counteracting inflammation and oxidation processes in an experimental Crohn's disease model, suggesting their potential as alternative therapeutic strategies for IBD.

Antinociceptive and Anti-Inflammatory Activities of Acetonic Extract from Bougainvillea x buttiana (var. Rose).

Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory properties and its potential action mechanisms. Methods: Analgesic and anti-inflammatory activities were evaluated using three murine pain models and two acute inflammation models. In vitro, the ability of the extract to inhibit proteolytic activity and the activities of the enzymes phospholipase A2 (PLA2) and cyclooxygenase (COX) were evaluated. In silico analysis was performed to predict the physicochemical and Absorption, distribution, metabolism, and excretion (ADME) profiles of the compounds previously identified in BxbRAE-100%. Results: In vivo BxbRAE-100% decreased the nociceptive behaviors in the writhing model, the tail immersion, and the formalin test, suggesting that the extract has the potential to relieve pain at peripheral and central levels. Additionally, topical or oral BxbRAE-100% treatment reduced dose-dependent 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation and carrageenan-induced paw edema, respectively. In vitro, BxbRAE-100% significantly inhibited proteolytic activity and PLA2, COX-1 and COX-2 activities. In silico, the compounds previously identified in BxbRAE-100% met Lipinski's rule of five and showed adequate ADME properties. Conclusions: These results support the use of B. x buttiana in Traditional Mexican Medicine and highlight its potential for the development of new treatments for pain and inflammation.

The Development and Pre-Clinical Anti-Inflammatory Efficacy of a New Transdermal Ureasil-Polyether Hybrid Matrix Loaded with Flavonoid-Rich Annona muricata Leaf Extract.

This study aimed to develop a novel ureasil-polyether transdermal hybrid matrix (U-PEO) loaded with Annona muricata concentrated extract (AMCE), which exhibits potent anti-inflammatory activity. The extract was obtained by maceration, a method that allowed for the extraction of a high concentration of flavonoids (39.27 mg/g of extract). In vivo tests demonstrated that 10 mg/kg of AMCE inhibited inflammation for 6 h. The physicochemical characterization of U-PEO with AMCE was conducted via a thermogravimetric analysis (TGA), while its surface was recorded using atomic force microscopy (AFM). The in vitro macroscopic swelling and release tests demonstrated the hydrophilic profile of the material and the percentage of AMCE released. The TGA results demonstrated that the system exhibited physical compatibility due to the thermal stability of U-PEO. Additionally, the AFM analysis revealed a rough and porous surface, with a particular emphasis on the system with AMCE. The release resulted in the liberation of 23.72% of AMCE within 24 h. Finally, the preclinical tests demonstrated that U-PEO with AMCE was also capable of effectively inhibiting inflammation for 6 h, a duration comparable to that of a commercial formulation. The results permit the advancement of the study towards the development of a transdermal system, thereby rendering its application in clinical studies feasible.