High-Throughput Molecular Modeling and Evaluation of the Anti-Inflammatory Potential of Açaí Constituents against NLRP3 Inflammasome.

The search for bioactive compounds in natural products holds promise for discovering new pharmacologically active molecules. This study explores the anti-inflammatory potential of açaí (Euterpe oleracea Mart.) constituents against the NLRP3 inflammasome using high-throughput molecular modeling techniques. Utilizing methods such as molecular docking, molecular dynamics simulation, binding free energy calculations (MM/GBSA), and in silico toxicology, we compared açaí compounds with known NLRP3 inhibitors, MCC950 and NP3-146 (RM5). The docking studies revealed significant interactions between açaí constituents and the NLRP3 protein, while molecular dynamics simulations indicated structural stabilization. MM/GBSA calculations demonstrated favorable binding energies for catechin, apigenin, and epicatechin, although slightly lower than those of MCC950 and RM5. Importantly, in silico toxicology predicted lower toxicity for açaí compounds compared to synthetic inhibitors. These findings suggest that açaí-derived compounds are promising candidates for developing new anti-inflammatory therapies targeting the NLRP3 inflammasome, combining efficacy with a superior safety profile. Future research should include in vitro and in vivo validation to confirm the therapeutic potential and safety of these natural products. This study underscores the value of computational approaches in accelerating natural product-based drug discovery and highlights the pharmacological promise of Amazonian biodiversity.

Monoterpene antifungal activities: evaluating geraniol, citronellal, and linalool on Candida biofilm, host inflammatory responses, and structure-activity relationships.

Introduction: Despite the rising concern with fungal resistance, a myriad of molecules has yet to be explored. Geraniol, linalool, and citronellal are monoterpenes with the same molecular formula (C10H18O), however, neither the effect of these compounds on inflammatory axis induced by Candida spp. nor the antibiofilm Structure-Activity Relationship (SAR) have been well-investigated. Herein we analyzed geraniol, linalool and citronellal antifungal activity, cytotoxicity, and distinctive antibiofilm SAR, also the influence of geraniol on Candida spp induced dysregulated inflammatory axis, and in vivo toxicity. Methods: Minimal inhibitory (MIC) and fungicidal (MFC) concentrations against Candida spp were defined, followed by antibiofilm activity (CFU-colony forming unit/mL/g of dry weight). Cytotoxic activity was assessed using human monocytes (THP-1) and oral squamous cell (TR146). Geraniol was selected for further analysis based on antifungal, antibiofilm and cytotoxic results. Geraniol was tested using a dual-chamber co-culture model with TR146 cells infected with C. albicans, and THP-1 cells, used to mimic oral epithelium upon fungal infection. Expression of Candida enzymes (phospholipase-PLB and aspartyl proteases-SAP) and host inflammatory cytokines (interleukins: IL-1ß, IL-6, IL-17, IL-18, IL-10, and Tumor necrosis factor-TNF) were analyzed. Lastly, geraniol in vivo toxicity was assessed using Galleria mellonella. Results: MIC values obtained were 1.25-5 mM/mL for geraniol, 25-100 mM/mL for linalool, and 100-200 mM/mL for citronellal. Geraniol 5 and 50 mM/mL reduced yeast viability during biofilm analysis, only 500 mM/mL of linalool was effective against a 72 h biofilm and no biofilm activity was seen for citronellal. LD50 for TR146 and THP-1 were, respectively: geraniol 5.883 and 8.027 mM/mL; linalool 1.432 and 1.709 mM/mL; and citronellal 0.3006 and 0.1825 mM/mL. Geraniol was able to downregulate expression of fungal enzymes and host pro-inflammatory cytokines IL-1ß, IL-6, and IL-18. Finally, safety in vivo parameters were observed up to 20 mM/Kg. Discussion: Despite chemical similarities, geraniol presented better antifungal, antibiofilm activity, and lower cytotoxicity when compared to the other monoterpenes. It also showed low in vivo toxicity and capacity to downregulate the expression of fungal enzymes and host pro-inflammatory cytokines. Thus, it can be highlighted as a viable option for oral candidiasis treatment.

Fixed oil from the Caatinga palm Syagrus coronata with effect on Complete Freund's Adjuvant (CFA)-induced arthritis.

Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.

Wound healing potential and anti-inflammatory action of extracts and compounds of Myrciaria plinioides D. Legrand leaves.

Wounds or chronic injuries are associated with high medical costs so, develop healing-oriented drugs is a challenge for modern medicine. The identification of new therapeutic alternatives focuses on the use of natural products. Therefore, the main goal of this study was to evaluate the healing potential and anti-inflammatory mechanism of action of extracts and the main compounds derived from Myrciaria plinioides D. Legrand leaves. The antimicrobial activity of leaf extracts was analyzed. Cell viability, cytotoxicity and genotoxicity of plant extracts and compounds were also assessed. Release of pro- and anti-inflammatory cytokines and TGF-ß by ELISA, and protein expression was determined by Western Blot. The cell migration and cell proliferation of ethanol and aqueous leaf extracts and p-coumaric acid, quercetin and caffeic acid compounds were also evaluated. The aqueous extract exhibited antibacterial activity and, after determining the safety concentrations in three assays, we showed that this extract induced p38-α MAPK phosphorylation and the same extract and the p-coumaric acid decreased COX-2 and caspase-3, -8 expression, as well as reduced the TNF-α release and stimulated the IL-10 in RAW 264.7 cells. In L929 cells, the extract and p-coumaric acid induced TGF-ß release, besides increasing the process of cell migration and proliferation. These results suggested that the healing properties of Myrciaria plinioides aqueous extract can be associated to the presence of phenolic compounds, especially p-coumaric acid, and/or glycosylated metabolites.

Exploring the biological activities and potential therapeutic applications of agro-industrial waste products through non-clinical studies: A systematic review.

The latent potential of active ingredients derived from agro-industrial waste remains largely untapped and offers a wealth of unexplored resources. While these types of materials have applications in various fields, their ability to benefit human health needs to be further explored and investigated. This systematic review was conducted to systematically evaluate non-clinical studies that have investigated the biological effects of fractions, extracts and bioactive compounds from agro-industrial wastes and their potential therapeutic applications. Articles were selected via PubMed, Embase and Medline using the descriptors (by-products[title/abstract]) AND (agro-industrial[title/abstract]). The systematic review was registered in the International Prospective Register of Systematic Reviews (Prospero) under the number CRD42024491021. After a detailed analysis based on inclusion and exclusion criteria, a total of 38 articles were used for data extraction and discussion of the results. Information was found from in vitro and in vivo experiments investigating a variety of residues from the agro-industry. The studies investigated peels, pomace/bagasse, pulp, seeds, aerial parts, cereals/grains and other types of waste. The most studied activities include mainly antioxidant and anti-inflammatory effects, but other activities such as antimicrobial, cytotoxic, antiproliferative, antinociceptive, hypoglycemic, antihyperglycemic and anticoagulant effects have also been described. Finally, the studies included in this review demonstrate the potential of agro-industrial waste and can drive future research with a focus on clinical application.

Efficacy of preoperative and postoperative medications in reducing pain after non-surgical root canal treatment: an umbrella review.

OBJECTIVE: This study analyzed, using an umbrella review, existing systematic reviews on medications to prevent and control postoperative endodontic pain to guide professionals in choosing the most effective drug. MATERIALS AND METHODS: An electronic search in the PubMed (MEDLINE), LILACS, SciELO, EMBASE, Scopus, Web of Science, Cochrane Reviews, and Data Archiving and Networked Services (DANS) databases retrieved 17 systematic reviews. The study included only systematic reviews of clinical trials with or without meta-analyses evaluating effectiveness of medications in reducing pain after non-surgical endodontic treatment. RESULTS: The evidence showed that steroidal and non-steroidal anti-inflammatory drugs and opioids effectively controlled pain within six to 24 h. CONCLUSIONS: Dexamethasone, prednisolone, paracetamol, and mainly ibuprofen provided higher postoperative pain relief. The quality of evidence of the reviews ranged from very low to high, and the risk of bias from low to high, suggesting the need for well-designed clinical trials to provide confirmatory evidence. CLINICAL RELEVANCE: This review emphasizes the efficacy of developing protocols for pain control after endodontic therapy.

Nephroprotective effect of pioglitazone in a Wistar rat model of adenine­induced chronic kidney disease.

Chronic kidney disease (CKD) is a progressive disease with a high mortality rate and a worldwide prevalence of 13.4%, triggered by various diseases with high incidence. The aim of the present study was to investigate the anti-inflammatory and antifibrotic effect of pioglitazone on kidney in an adenine-induced Wistar rats and the mechanisms possibly involved. CKD was induced in 40 rats. Rats were divided into two groups, which were split into the following sub-groups: i) Therapeutic (pioglitazone administered after renal damage) divided into intact (healthy), adenine (CKD) and adenine/pioglitazone (treatment) and ii) prophylactic (adenine and pioglitazone administered at the same time) split into intact (healthy), adenine (CKD), endogenous reversion (recovery without treatment), adenine/pioglitazone (treatment) and pioglitazone sub-groups. Reverse transcription-quantitative PCR (collagen I, α-SMA and TGF-ß), and hematoxylin-eosin, Masson's trichrome and Sirius red staining were performed to measure histological markers of kidney damage, also the serum markers (urea, creatinine and uric acid) were performed, for analyze the effects of pioglitazone. In the adenine/pioglitazone rats of the therapeutic group, renal function parameters such as eGFR increased and serum creatinine decreased from those of untreated rats (CKD), however the renal index, serum urea, abnormalities in renal morphology, inflammatory cells and relative gene expression of collagen I, α-SMA and TGF-ß did not change relative to the CKD rats. In adenine/pioglitazone rats, extracellular matrix collagen accumulation was significantly lower than the CKD rats. On the other hand, in adenine/pioglitazone rats of the prophylactic group, the renal index, creatinine, urea, uric acid serum and relative gene expression of collagen I, α-SMA, and TGF-ß were significantly lower, as well as the presence of 2,8-dihydroxyadenine crystals, and extracellular matrix collagen compared with CKD rats. In addition, the eGFR in the treatment group was similar to healthy rats, renal morphology was restored, and inflammatory cells were significantly lower. In conclusion, pioglitazone has a nephroprotective effect when administered in the early stages of kidney damage, reducing inflammatory and fibrotic processes and improving glomerular filtration rate. Furthermore, in the late phase of treatment, a tendency to decrease creatinine and increase eGFR was observed.

Anti-inflammatory action of silver nanoparticles in vivo: systematic review and meta-analysis.

The aim of this study was to systematically review the literature to investigate whether silver nanoparticles (AgNPs) have an anti-inflammatory effect in vivo. The guidelines of PRISMA were applied, and a registration was made in PROSPERO. A personalized search of the PubMed, Web of Science, Scopus, Embase, Lilacs, and Google Scholar databases was conducted in September 2023. For the data analysis, the inverse variance in the random effects model was used. The tools of SYRCLE and GRADE were used to assess the risk of bias and the certainty of evidence, respectively. From the 9185 identified studies, 5685 duplicate studies were excluded; 52 were read in full text, and 7 were included in this review. Six studies were evaluated by the meta-analysis, and an increase in anti-inflammatory molecules (SMD -5.22; PI [-6.50, -3.94]) and an increase in anti-inflammatory ones (SMD 5.75; PI [3.79, 7.72]) were observed. Qualitative analysis showed a reduction in pro-inflammatory proteins and in the COX-2 pathway. It was concluded that AgNPs present an anti-inflammatory action in vivo through mechanisms involving the reduction of pro-inflammatory molecules and proteins, the increase of anti-inflammatory molecules, and selective inhibition of the COX-2 pathway.

Prescription of non-steroidal anti-inflammatory and antirheumatic drugs in outpatient hypertensive patients.

BACKGROUND: It has been documented that NSAIDs (nonsteroidal anti-inflammatory and antirheumatic drugs) reduce the effectiveness of some antihypertensive drugs. OBJECTIVE: Analyze the prescription of NSAID and the variables associated in outpatients with hypertension and explore some characteristics of the physicians. MATERIAL AND METHODS: Cross-sectional study, included patients with hypertension from the Family Medicine Unit No. 24 in Mante, Tamaulipas. From the patients, sociodemographic data, clinical history and pharmacological treatments were obtained. From the physicians, sociodemographic and academic information were collected. RESULTS: Mean age of the patients was 63 ± 11 years and 31.7% were prescribed NSAIDs. When compare exposed versus non-exposed to NSAIDs, being in uncontrolled high blood pressure, uncontrolled hypertension, multimorbidity and polypharmacy. The variables associated to the prescription of NSAIDs were: uncontrolled hypertension, multimorbidity and polypharmacy. The 56.7% of the physicians were women, 83.3% with experience >10 years and 33.3% with current certification by the Council in Family Medicine. CONCLUSIONS: The inappropriate prescription of NSAIDs revealed the need to implement actions to mitigate the potential risk for the hypertension patients to present a complication.

ANTECEDENTES: Los antiinflamatorios y los antirreumáticos no esteroideos (AINE) disminuyen la eficacia de algunos antihipertensivos. OBJETIVO: Analizar el patrón de prescripción de AINE y las variables asociadas en pacientes ambulatorios con diagnóstico de hipertensión arterial, así como explorar algunas características de los médicos prescriptores. MATERIAL Y MÉTODOS: Estudio transversal de pacientes con hipertensión de la Unidad de Medicina Familiar 24 en Ciudad Mante, Tamaulipas. De los pacientes se registraron datos sociodemográficos, antecedentes patológicos y tratamientos farmacológicos; y de los médicos, información sociodemográfica y académica. RESULTADOS: La edad promedio de los pacientes fue de 63 ± 11 años, 31.7 % recibía AINE y al contrastarlos con quienes no los recibían, se identificó mayor proporción de obesidad, presión arterial más elevada, más casos en descontrol de la hipertensión arterial, multimorbilidad y polimedicación. Las variables asociadas a la prescripción de AINE fueron estar en descontrol de la hipertensión arterial, multimorbilidad y polimedicación; 56.7 % de los médicos prescriptores fue del sexo femenino, 83.3 % con antigüedad superior a 10 años y 33.3 % con certificación vigente. CONCLUSIONES: La prescripción inapropiada de AINE reveló la necesidad de implementar acciones para mitigar el riesgo potencial de los pacientes hipertensos de presentar una complicación.

Ferulic Acid: A Review of Mechanisms of Action, Absorption, Toxicology, Application on Wound Healing.

Ferulic acid is a widely distributed phenolic substance with diverse bioactive properties, which has been widely used in the pharmaceutical, food, and cosmetic industries. Wounds are complex skin lesions to treat and their treatment is long and costly. This encourages the search for alternative treatments, especially in the area of bioactive substances of natural origin. AIMS: This work aims to make a bibliographic survey on studies of the use of ferulic acid in the treatment of wounds. RESULTS: The studies found show that ferulic acid acts through different mechanisms of action such as antioxidant, anti-inflammatory, antimicrobial, collagen production, angiogenic, and reepithelialization effects. These properties act synergistically in different stages of healing, which differentiates it from conventional treatments. In addition, ferulic acid has dermal absorption, low skin metabolism, and low toxicity. CONCLUSION: Studies in this area are recent and further research is needed to expand the possibilities and therapeutic efficiency of ferulic acid in wound healing.

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.

Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

The Protective Effect of Juçara Fruit (Euterpe edulis Martius) Extracts on LPS-Activated J774 Macrophages.

This study investigated the anti-inflammatory effect of hydrophilic and lipophilic extracts from juçara fruits (Euterpe edulis Martius) through measurement of nitric oxide (NOx) and cytokines (IL-12p70, TNF-α, INF-γ, MCP-1, IL-6, and IL-10). J774 macrophages were stimulated with lipopolysaccharides (1 µg/mL) and treated with various concentrations (1-100 µg/mL) of juçara fruits extracts from crude extracts, and hexane, dichloromethane, ethyl acetate, and butanol fractions. Potential relationships between the phenolic composition of the extracts determined by LC-ESI-MS/MS and their anti-inflammatory capacity were also evaluated. Hexane and dichloromethane fractions inhibited NOx and IL-12p70 while increased IL-10. Hexane fractions also decreased IL-6 and IFN-γ production. Hexane and dichloromethane fractions showed a higher number of phenolic compounds (32 and 34, respectively) than the other extracts tested and were also the only ones that presented benzoic acid and pinocembrin. These results suggest juçara fruits compounds as potential anti-inflammatory agents, especially those of a more apolar nature.

Taming the storm: potential anti-inflammatory compounds targeting SARS-CoV-2 MPro.

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2 µM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19.

Priority list of pharmaceutical active compounds in aquatic environments of Mexico considering their occurrence, environmental and human health risks.

Pharmaceutical active compounds (PhACs) are detected pollutants in aquatic environments worldwide at concentrations ranging from ng L-1 to µg L-1. Currently, PhAC monitoring is poorly realized in Mexico. This study proposes a priority list of PhACs in Mexican aquatic environments, considering their occurrence and environmental and human health risks. Ecological risks were assessed as Risk Quotients (RQ) values using the PhAC concentrations detected in surface water, obtaining high risks (RQ > 1) against aquatic organisms, especially of naproxen, ibuprofen, diclofenac, acetaminophen, 17ß-estradiol, carbamazepine, ketoprofen, caffeine. In contrast, potential human health risks (RQH) were assessed on the Mexican population using the concentrations quantified in groundwater, demonstrating potential risks (RQH > 0.2) on the population, particularly of DCF and CBZ. Thus, a priority list of PhACs can be used as a reference for environmental monitoring in Mexican water supplies as well as PhACs monitoring in countries of the Caribbean region and Central America.

Anti-inflammatory and antiophidic effects of extract of Hymenaea eriogyne benth and structure-activity relationship prediction of the major markers in silico.

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea eriogyne Benth (Fabaceae) is popularly known as "Jatobá". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential. AIM OF THE STUDY: In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne. MATERIALS AND METHODS: The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and myeloperoxidase (MPO) activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on MPO activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used. RESULTS: The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50-200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO. CONCLUSION: This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.

Preemptive oral analgesia with steroidal and nonsteroidal anti-inflammatory drugs in periodontal surgery: a systematic review.

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries. Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out. Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8 mg, etoricoxib 90 mg or 120 mg and ketorolac 20 mg seems to be more effective for controlling post-operative pain than placebo. Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.

In vitro and In vivo Activity of a New N-Oxide Derivative for Acne Vulgaris Treatment.

INTRODUCTION: Furoxan and benzofuroxan are compounds containing an N-oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds. METHOD: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes), a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes, with a Minimum Inhibitory Concentration (MIC) value of 2 µg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 µg/mL. RESULTS: Measurements of Interleukin-1 beta (IL1-ß) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 µg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties. CONCLUSION: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.

Effects of apples (Malus domestica) and their derivatives on metabolic conditions related to inflammation and oxidative stress and an overview of by-products use in food processing.

Apple (Malus domestica) is the third most produced fruit worldwide. It is a well-known source of bioactive compounds mainly represented by hydroxycinnamic acids, flavan-3-ols, dihydrochalcones, dehydroascorbic acid, carotenoids, chlorogenic acid, epicatechin, and phloridzin. Due to the lack of a recent evaluation of the clinical trials associated with apple consumption, this review investigated the effects of this fruit on metabolic conditions related to inflammation and oxidative stress and reviewed the applications of apple waste on food products. Thirty-three studies showed that apples or its derivatives exhibit anti-inflammatory and antioxidant actions, improve blood pressure, body fat, insulin resistance, dyslipidemia, and reduce cardiovascular risks. Apples have a great economic impact due to its several applications in the food industry and as a food supplement since it has impressive nutritional value. Dietary fiber from the fruit pomace can be used as a substitute for fat in food products or as an improver of fiber content in meat products. It can also be used in bakery and confectionary products or be fermented to produce alcohol. Pomace phytocompounds can also be isolated and applied as antioxidants in food products. The potential for the use of apples and by-products in the food industry can reduce environmental damage.

Health-Promoting Potential of Mandarin Pomace Extracts Enriched with Phenolic Compounds.

The aim of this work was to assess the effect of in vitro human digestion on the chemical composition (carbohydrates and phenolic compounds) and bioactivity of hydro-alcoholic-acid pomace extracts from two mandarin varieties (Clemenule and Ortanique) by measuring their antioxidant, antidiabetic, anti-glycative, hypolipidemic, and anti-inflammatory properties. The phenolic compound profile showed that nobiletin was the main flavonoid found in the extracts and digests of Clemenule pomace and extract, while isosinensetin/sinensetin/tangeretin were the ones in the Ortanique samples. The digests of Clemenule and Ortanique extracts showed Folin reaction values of 9.74 and 9.20 mg gallic acid equivalents (GAE)/g of sample, ABTS values of 83.2 and 91.7 µmol Trolox equivalents (TE)/g of sample, and ORAC-FL values of 142.8 and 891.6 µmol TE/g of sample, respectively. Extracts (50-500 µg/mL) inhibited intracellular reactive oxygen species (ROS) formation in CCD-18Co cells under physiological and oxidative-induced conditions. Clemenule and Ortanique extract digests showed IC50 values of 13.50 and 11.07 mg/mL for α-glucosidase, 28.79 and 69.64 mg/mL for α-amylase, and 16.50 and 12.77 mg/mL for AGEs, and 2.259 ± 0.267 and 0.713 ± 0.065 mg/mL for pancreatic lipase inhibition, respectively. Ortanique extract (250-1000 µg/mL) inhibited the production of nitric oxide in RAW264.7 macrophages under inflammation-induced conditions, and intracellular ROS formation. In conclusion, altogether, the results supported the potential of mandarin extracts to be used as health promoters by reducing the risk of non-communicable chronic diseases.