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.

Research progress on association between macrophages and ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

Antitumor and immunomodulatory activity of fucoidan from the brown alga Lessonia trabeculata (Lessoniaceae) on breast cancer spheroids / Actividad antitumoral e inmunomoduladora de fucoidan del alga parda Lessonia trabeculata (Lessoniaceae) en esferoides de cáncer de mama

Abstract Introduction: The therapeutic benefits of the brown algae fucoidan in the treatment of breast cancer have attracted considerable interest in recent years. However, research using spheroids which provide relevant results in trials for antitumor and immunomodulatory products because they adequately simulate the tumor microenvironment, is limited. Objective: To evaluate the antitumor and immunomodulatory activity of Lessonia trabeculata fucoidan (LtF), native to the Peruvian Sea, on two types of multicellular tumor spheroids. Methods: The study was conducted from January to December 2021. Two types of spheroides were elaborated: from 4T1 tumor cells (MTS), and from 4T1 tumor cells+mouse splenocytes (MTSs). The antitumor activity of LtF was evaluated in MTS by quantifying cell viability with MTT. Immunomodulatory activity was determined in MTSs using the IC50 for two types of treatment: simple, fucoidan alone (LtF) and combined, fucoidan+doxorubicin (LtF+Dox). Pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-10, TGF-β) cytokine production was quantified by sandwich ELISA 72 h after treatment. Dox was used as positive control in all assays. Results: LtF exerted antitumor activity as evidenced by increased necrotic zone and cell debris formation compared to the untreated control. Antitumor activity was concentration dependent between 100 and 6 000 μg/ml. In MTSs, simple treatment increased IL-6 and decreased IL-10 and TGF-β production. The combined treatment significantly reduced TGF-β production. In both treatments and Dox, there was an increase in IL-6 compared to the untreated control. The highest production of IL-10 and TGF-β was observed in the untreated control, compatible with a highly immunosuppressive tumor microenvironment. Conclusions: LtF is a good candidate for the treatment of breast cancer and can immunomodulate the tumor microenvironment alone or in combination with Dox.

Resumen Introduccción: Los beneficios terapéuticos del fucoidan de algas pardas en el tratamiento del cáncer de mama han despertado gran interés en los últimos años. Sin embargo, las investigaciones con esferoides son limitadas, éstos proporcionan resultados relevantes en ensayos de productos antitumorales e inmunomoduladores porque simulan adecuadamente el microambiente tumoral. Objetivo: Evaluar la actividad antitumoral e inmunomoduladora del fucoidan de Lessonia trabeculata (LtF), nativa del Mar Peruano, en dos tipos de esferoides tumorales multicelulares. Métodos: El estudio se realizó de enero a diciembre de 2021. Se elaboraron dos tipos de esferoides: con células tumorales 4T1 (MTS) y con células tumorales 4T1+esplenocitos de ratón (MTSs). La actividad antitumoral de LtF se evaluó en MTS cuantificando la viabilidad celular con MTT. La inmunomodulación se determinó en MTSs utilizando la IC50 para dos tipos de tratamiento: simple, fucoidan solo (LtF) y combinado, fucoidan+doxorubicina (LtF+Dox). La producción de citoquinas proinflamatorias (TNF-α, IL-6) y antiinflamatorias (IL-10, TGF-β) se cuantificó mediante ELISA sándwich 72 h post-tratamiento. En todos los ensayos se utilizó Dox como control positivo. Resultados: En los MTS, el LtF ejerció actividad antitumoral evidenciada por aumento de la zona necrótica y formación de restos celulares respecto al control no tratado. La actividad antitumoral fue concentración-dependiente entre 100 y 6 000 μg/ml. En los MTSs, con el tratamiento simple se incrementó IL-6 y disminuyeron IL-10 y TGF-β. El tratamiento combinado redujo significativamente la producción de TGF-β. Los dos tratamientos y Dox incrementaron IL-6 respecto al control no tratado. La mayor producción de IL-10 y TGF-β se observó en los no tratados, compatible con un microambiente tumoral altamente inmunosupresor. Conclusiones: El LtF es un buen candidato para tratar el cáncer de mama y puede inmunomodular el microambiente tumoral solo o en combinación con Dox.

Potential Comparison of Anti-inflammatory Activities of Quercetin and Diclofenac Mouthwash Formulations

Introduction: Periodontitis is a pandemic, with about 14 percent of people worldwide already suffering from severe periodontitis. Early intervention in the disease could probably reduce its progression and eliminate the need for the extraction of affected teeth. Quercetin is a probable candidate as it has exemplary anti-inflammatory properties. The presence of phenolic hydroxyl groups in them greatly contributes to their antioxidant and anti-inflammatory activities. Objectives: The study introduces the formulation of Quercetin mouthwash and assesses its anti-inflammatory properties in comparison to Diclofenac sodium. Methods: Quercetin mouthwash was prepared using a commercially procured bioactive agent. One standard nonsteroidal anti-inflammatory drug, Diclofenac was used as a reference drug. The percentage inhibition of protein denaturation was calculated and its anti-inflammatory properties were evaluated through Bovine Serum Albumin Assay and Egg Albumin Assay. Results: Quercetin mouthwash showed parallel anti-inflammatory properties and showed a proportionate increase in anti-inflammatory properties with the increase in the concentration of the mouthwash. Comparable inhibition of protein denaturation at 10µl and 50µl concentrations with a proportionate variation of 1 percent (p>0.05) to the control in Egg Albumin Assay and 47 percent and 83 percent denaturation at 10µl and 50µl of Bovine Serum Albumin Assay were observed. Conclusion: Quercetin mouthwash has shown significant anti-inflammatory activity and hence is considered a potent anti-inflammatory agent comparable to Diclofenac sodium. It is found to be a suitable agent as an oral formulation for reducing the progression of inflammatory conditions(AU)

Introducción: La periodontitis es una pandemia, ya que alrededor del 14 por ciento de las personas en todo el mundo padecen periodontitis grave. Una intervención precoz en la enfermedad podría, probablemente, reducir su progresión y eliminar la necesidad de extraer los dientes afectados. La quercetina es un candidato probable, ya que tiene propiedades antiinflamatorias ejemplares. Su presencia de grupos hidroxilos fenólicos contribuye en gran medida a sus actividades antioxidantes y antiinflamatorias. Objetivos: El estudio presenta la formulación del colutorio de quercetina y evalúa sus propiedades antiinflamatorias en comparación con el diclofenaco sódico. Métodos: Se preparó un colutorio de quercetina, utilizando un agente bioactivo obtenido comercialmente. Se utilizó como fármaco de referencia un antiinflamatorio no esteroideo estándar, el diclofenaco. Se calculó el porcentaje de inhibición de la desnaturalización de proteínas y se evaluaron sus propiedades antiinflamatorias mediante ensayo con albúmina de suero bovino y con albúmina de huevo. Resultados: El colutorio de quercetina mostró propiedades antiinflamatorias paralelas y mostró un aumento proporcional de las propiedades antiinflamatorias con el aumento de la concentración del colutorio. Se observó una inhibición comparable de la desnaturalización de proteínas a concentraciones de 10µl y 50µl con una variación proporcional del 1 por ciento (p > 0,05), respecto al control en el ensayo de albúmina de huevo y una desnaturalización del 47 por ciento y 83 por ciento a 10µl y 50µl del ensayo de albúmina de suero bovino. Conclusiones: El enjuague bucal de quercetina ha mostrado una actividad antiinflamatoria significativa, por lo que se considera un potente agente antiinflamatorio comparable al diclofenaco sódico. Se considera un agente adecuado como formulación oral para reducir la progresión de las afecciones inflamatorias(AU)

Aplicação de ácido hialurônico e corticoide através de uma punção guiada por ultrassonografia no tratamento de disfunção da articulação temporomandibular: relato de caso / Hyaluronic and corticoid application through an ultrasound-guided puncture in the treatment of temporomandibular joint dysfunctions: case report / Aplicación de ácido hialurónico y corticoide a través de una punción guiada por ecografía en el tratamiento de la disfunción de la articulación temporomandibular: informe de un caso

Introdução: As Disfunções temporomandibulares (DTM) incluem desordens dos músculos da mastigação, das articulações temporomandibulares e da inervação local, frequentemente associadas a dor orofacial e que resultam em mioartropatias do Sistema Mastigatório. A tendência atual tende a começar com tratamento conservador e progredir a procedimentos mais invasivos na falha dos tratamentos iniciais. Relato de caso: O presente relato visa mostrar o resultado de uma técnica invasiva para o tratamento de uma DTM grave, com a aplicação do ácido hialurônico e de corticoide através de uma punção guiado por ultrassonografia. A paciente apresentava dor crônica e perda importante de peso devido a limitação da abertura da boca. A RM demonstrou disfunção das ATMs, com sinais de deslocamento parcial do disco direito anteromedialmente. Foi realizada a aplicação bilateral intra-articular de ácido hialurônico e de corticoide através de uma punção guiado por ultrassonografia. Considerações Finais: A associação destas classes na punção de ATMs ainda não está bem estabelecida havendo necessidade de estudos complementares para avaliar eficácia, como este relato de caso, que se mostrou favorável com grande melhora clínica da paciente... (AU)

Introduction: Temporomandibular dysfunctions (TMD) include disorders of the masticatory muscles, temporomandibular joints, and local innervation, often associated with orofacial pain and resulting in myoarthropathies of the masticatory system. The current trend tends to begin with conservative treatment and progress to more invasive procedures if the initial treatments fail. Case Report: The present report aims to show the result of an invasive technique for the treatment of a severe TMD, with the application of hyaluronic acid and corticoid through an ultrasound-guided puncture. The patient presented with chronic pain and significant weight loss due to limited mouth opening. MRI demonstrated TMJ dysfunction, with signs of partial anteromedial dislocation of the right disc. Bilateral intra-articular application of hyaluronic acid and corticoid was performed through an ultrasound guided puncture. Final considerations: The association of these classes in TMJ puncture is still not well established, and further studies are needed to evaluate efficacy, as in this case report, which proved favorable, with great clinical improvement for the patient... (AU)

Introducción: Los trastornos temporomandibulares (TTM) incluyen trastornos de los músculos masticatorios, de las articulaciones temporomandibulares y de la inervación local, a menudo asociados a dolor orofacial y que dan lugar a mioartropatías del sistema masticatorio. La tendencia actual es comenzar con un tratamiento conservador y progresar hacia procedimientos más invasivos al fracasar los tratamientos iniciales. Informe de un caso: El presente informe pretende mostrar el resultado de una técnica invasiva para el tratamiento de un TTM severo, con la aplicación de ácido hialurónico y corticoide a través de una punción guiada por ecografía. El paciente presentaba dolor crónico y una importante pérdida de peso debido a la limitación de la apertura bucal. La RMN demostró una disfunción de la ATM, con signos de dislocación parcial del disco derecho anteromedialmente. Se realizó la aplicación intraarticular bilateral de ácido hialurónico y corticoide mediante una punción guiada por ecografía. Consideraciones finales: La asociación de estas clases en la punción de la ATM aún no está bien establecida y se necesitan más estudios para evaluar la eficacia, como en el reporte de este caso, que resultó favorable con gran mejoría clínica del paciente... (AU)

Actividad antiinflamatoria in vitro de Plantago major L. y Piper aduncum L. sobre la fosfolipasa A2 del veneno de la serpiente Lachesis muta muta / In vitro anti-inflammatory activity of Plantago major L. and Piper aduncum L. on phospholipase A2 from the venom of snake Lachesis muta muta

Objetivo. Evaluar la actividad inhibitoria in vitro de los extractos de Plantago major «llantén» y Piper aduncum «matico» sobre Fosfolipasa A2 (PLA2) del veneno de la serpiente Lachesis muta muta. Materiales y métodos. Esta investigación fue de tipo explicativa con diseño experimental. Se recolectaron hojas de P. major y P. aduncum en la provincia de Huarochirí en Lima, Perú. Se prepararon extractos alcohólicos diluidos en agua destilada y se realizaron los ensayos fitoquímicos, la cuantificación de fenoles y flavonoides, la cromatografía de capa fina (CCF) en celulosa y la actividad enzimática con PLA2. Se analizó la capacidad de inhibir la PLA2 con los extractos en estudio y sus fracciones. Para el análisis estadístico se utilizó la prueba de Kruskal Wallis y comparaciones múltiples de Bonferroni. Resultados. Tanto en P. major como en P. aduncum se identificó cualitativamente la presencia de fenoles, flavonoides y taninos; además, P. aduncum presentó saponinas. La inhibición de la actividad de la PLA2 del veneno por el extracto total de P. major fue del 45,3%, y sus fracciones mostraron valores de inhibición: LLF-1 con 31,1%, LLF-2 con 66,3% y LLF-3 con 65,5%. En P. aduncum, los valores de inhibición para el extracto total fueron de 86,9%, y sus fracciones presentaron inhibiciones: MF-1 con 34,3%, MF-2 con 67,1% y MF-3 con 54,9%. El análisis estadístico demostró diferencias significativas en la inhibición de la PLA2 (p=0,009) por los extractos. Conclusión. Los ensayos realizados demostraron una asociación entre el efecto antiinflamatorio de los extractos y la inhibición de la PLA2.

Objective. To evaluate the in vitro inhibitory activity of Plantago major "llantén" and Piper aduncum "matico" extracts on phospholipase A2 (PLA2) from the venom of the snake Lachesis muta muta. Materials and methods. We carried out an explanatory study with experimental design. Leaves of P. major and P. aduncum were collected in the province of Huarochirí in Lima, Peru. Then, we prepared alcoholic extracts diluted in distilled water and conducted phytochemical assays, quantification of phenols and flavonoids, thin layer chromatography (TLC) on cellulose and enzymatic activity with PLA2. The ability to inhibit PLA2 with the extracts under study and their fractions was analyzed. The Kruskal Wallis test and Bonferroni multiple comparisons were used during statistical analysis. Results. Phenols, flavonoids and tannins were qualitatively identified in both P. major and P. aduncum; in addition, P. aduncum presented saponins. The inhibition of PLA2 activity of the venom by the total extract of P. major was 45.3%, and its fractions showed the following inhibition values: 31.1% for LLF-1, 66.3% for LLF-2 and 65.5% for LLF-3. The inhibition values for the total extract of P. aduncum were 86.9%, and its fractions showed the following inhibition rates: 34.3% for MF-1, 67.1% for MF-2 and 54.9% for MF-3. Statistical analysis showed significant differences in the inhibition of PLA2 (p=0.009) by the extracts. Conclusion. The tests demonstrated an association between the anti-inflammatory effect of the extracts and PLA2 inhibition.

Evaluation of cell adhesion molecules (LFA-1 and L-selectin) in ankylosing spondylitis patients after treatment with ?-D-mannuronic acid (M2000)

Background & objectives: To examine ?-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). Methods: To investigate the molecular consequences of ?-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique. Results: The LFA-1 expression in patients with AS was higher than controls (P=0.046). The LFA-1 expression after 12 wk therapy with ?-D-mannuronic acid was meaningfully decreased (P=0.01). After 12 wk treatment with ?-D-mannuronic acid, the frequency of CD62L-expressing CD4+ T cells in patients with AS, was not considerably altered, compared to the patients before therapy (P=0.5). Furthermore, after 12 wk therapy with ?-D-mannuronic acid, L-selectin expression levels on CD4+ T-cells in patients with AS, were not remarkably changed, compared to the expression levels of these in patients before treatment (P=0.2). Interpretation & conclusions: The results of this study for the first time showed that ?-D-mannuronic acid can affect events of adhesion cascade in patients with AS. Moreover, ?-D-mannuronic acid presented as an acceptable benefit to AS patients and could aid in the process of disease management

Jatropha tanjorensis Euphorbiaceae Ethanolic Leaves Extract Reverses Phenylhydrazine Induced Haematological Alterations in Albino Wistar Rats

Introduction: Phenylhydrazine has been used in many studies to evaluate its modulatory effects in various biochemical parameters in whole blood and red blood cell lysate. Jatropha tanjorensis Euphorbiaceae have high antioxidants properties; its leaves phytochemical analysis shows the presence of flavonoids, tanins, terpenoids, saponis. This study investigated the ameliorative effects of Jatropha tanjorensis Euphorbiaceae on phenylhydrazine induced haematological alterations in albino Wistar rats. Materials and Methods: Wistar rats of both sexes (180-200g) were divided into 4 groups (n=5). Group 1 received rat chow; Group 2 received (200 mg/kg) of J. tanjorensis orally. Group 3 received phenylhydrazine only (10 mg/kg). Group 4 received phenylhydrazine (10 mg/kg) + J. tanjorensis (250 mg/kg). All animals were allowed free access to clean drinking water and normal rat chow ad libitum for 35 days. After which animals were sacrificed and blood samples collected for biochemical analysis. Results: Results obtained showed that phenylhydrazine induced normochromic anemia with significant increase in white blood cell count, and neutrophil counts, eosinophils (insignificant) count with a significant reduction in lymphocyte count. However, J. tanjorensis extract reversed the adverse haematological changes induced by phenylhydrazine. Conclusion: In conclusion, Jatropha tanjorensis Euphorbiaceae demonstrated antioxidant, anti-inflammatory, and anti-thrombotic effects and reversed the haematological alterations brought upon by phenylhydrazine administration.

Effect of Hayani Date (Phoenix dactylifera L) Peels on Blood Sugar, Blood Lipids, Liver and Kidney Functions, and Inflammation in Diabetic Rats

This study aimed to investigate the effect of Hayani date peel powder and its methanolic extract on glycemia and lipidemia in streptozotocin-induced diabetic rats as well as their effects on kidney and liver functions in addition to their anti-inflammatory activity. Twenty-four rats were used in this study, six of them served as normal control (group 1) which continued feeding on the basal diet, while the remaining 18 rats were injected with streptozotocin (50mg/kg) to induce diabetes. The diabetic rats were divided into three groups (6 rats each), one of them feeding on the basal diet only which acted as diabetic control (group 2), another group fed on the basal diet and treated orally with the peel extract in a concentration of 250 mg/kg body weight (group 3), while the third group was treated with peel powder merged in the basal diet with a concentration of 5% w/w (group 4). The results showed that the extract and the powder of the peels significantly decreased the blood glucose, glycated hemoglobin (HbAlc), total cholesterol (TC), total triglycerides (TG), low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, and uric acid as well as cyclooxygenase-2 (COX-2), prostaglandin 2 (PGE2), tumor necrosis factor alpha (TNF-?), interleukin 1B (IL-1?), and inducible nitric oxide synthase (iNOS) levels. In contrast, significant increases in serum insulin, high density lipoprotein cholesterol (HDL-c), and albumin were noticed in comparison to diabetic control. Generally, the peel extract was more effective than the peel powder. It is recommended by eating the whole fruit of date without peeling.

Anti-inflammatory Assessment of Methanol Extract of Acalypha ciliata Leaves and It’s Leucocyte Mobilization in Adult Wistar Rats

Aim: The study's objective was to examine the anti-inflammatory activity and leucocyte mobilization of a methanol extract of leaves from Acalypha ciliata in adult Wistar rats. Study Design: Egg albumin-induced edema was used for anti-inflammatory test and leucocyte mobilization test was carried out to check for total leucocyte cout and differentials. Place and Duration of the Study: This original study was conducted between January and June 2013 at the Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria Nsukka. Methology: The pulverized leaf of Acalypha ciliata was extracted using cold maceration, and the Treas and Evans technique of phytochemical screening was used. The anti-inflammatory study was conducted using the method of Winter et al., and the acute toxicity study was assessed using Lorke's method. ANOVA was used to statistically examine the collected data. Results: Preliminary phytochemical screening revealed the presence of flavonoids, alkaloids, soluble carbohydrates, phenols, glycosides, saponins, terpenoids and steroids. Flavonoids, Alkaloids, and Soluble carbohydrates appeared in abundant concentration (2199.76±10.81, 2141.6±7.583, 913±21.06). Acute toxicity tests showed no toxicity and mortality at doses up to 5000 mgkg-1. Anti-inflammatory study revealed that group treated with 100, 200 and 400 mg/kg b.w of extract significantly (P =0.05) and in a dose dependant manner decreased in TLC when compared with normal control. Moreover, the group treated with 100,200,400 mg/kg b.w of extract and reference drug(Indometacin) mobilized the leucocyte at the rate of 36, 22, 12 and 62 % respectively. A significant (P = 0.05) reduction in the mean paw oedema was observed for all the treatment groups from 1 hour to 5 hours when compared to the toxic group. Conclusion: As a result of this study's findings, it can be concluded that methanol extract of the Acalypha ciliata leaf has anti-inflammatory characteristics. High dosages of the extract resulted in a better decrease of oedema and an increase in leukocyte mobilization in response to agar suspension than low doses. Many anti-inflammatory herbs and substances alter inflammatory reactions by hastening the breakdown of or reversing the effect of the inflammatory mediators. The plant's anti-inflammatory properties could potentially result from the interaction of different photochemical substances present. The findings suggest that, if used, the plant may serve as a source of anti-inflammatory compounds.

Clinician's dilemma: Naproxen-induced liver injury

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

A new horizon in the prescription pattern of drugs for osteoarthritis in a tertiary care hospital: A prospective observational study

Background: Osteoarthritis (OA) is a significant contributor to chronic pain, mainly affecting lower extremity joints like the knee and hip, and causing considerable impairment in elderly individuals. OA treatment focuses on easing discomfort and enhancing mobility. Despite their adverse unfavorable effects, non-steroidal anti-inflammatory medications (NSAIDs) are frequently used for symptom alleviation. However, there is still a need for secure and efficient alternative therapies that could provide OA patients with both symptomatic relief and disease-modifying benefits. Despite the indisputable fact that the disease has a substantial socioeconomic impact on patients, there is not much research available to reflect on the medicine prescription pattern in OA. Aim and Objectives: The objectives of this study were to assess the prescription pattern and their rationality in patients with OA in a tertiary care hospital. Materials and Methods: A cross-sectional, prospective, and observational study conducted in the orthopedics department for all newly diagnosed and old treated patients with OA. Around 350 patients were taken into the study and their prescriptions were scrutinized. Descriptive statistics were used to analyze the data and present it as percentages. Results: Over 61.7% of females were affected compared to 38.3% of males with OA. The knee joint (76.2%) followed by the hip joint (13.7%) were the most common joints involved. Aceclofenac and diclofenac were the most common NSAIDs used in the patients, whereas piroxicam was the least prescribed drug. Gastroprotective agents, calcium supplements, and SYSDOA were the commonest adjuvants used in the treatment of OA patients. Conclusions: Even though NSAIDs are favored, SYSDOA and non-pharmacological treatments such as lifestyle changes, and frequent mild exercise have changed the treatment plan for OA

Diagnosis of a Case of Hepatotoxicity Due to Drugs and Herbal Supplements in a Hospital in Pasto, Colombia

The liver is a crucial organ in metabolism, and some substances can induce toxic hepatitis with high morbidity and mortality. Chemical and drug-induced liver disease is a diagnostic and therapeutic challenge since it requires extension studies to rule out other entities. We present the case of a 51-year-old female patient without underlying comorbidities, admitted due to symptoms of two-day evolution consisting of progressive jaundice, diarrheal episodes without acholia, or any other additional manifestation. Her condition was caused by the intake of nimesulide, two tablets a day for two days, for pain secondary to a mandibular cyst diagnosed in previous days. During her admission to the emergency room, the patient described chronic consumption of Herbalife® products daily for four years. She presented with elevated transaminases, prolonged prothrombin time (PT), and direct hyperbilirubinemia. Infectious and immunological diseases were ruled out. We decided to start antibiotic and vitamin K coverage. Finally, and by exclusion, a liver biopsy suggested an inflammatory process compatible with drug-induced hepatitis. The woman evolved favorably when the medication and dietary supplement were discontinued. In conclusion, this case constitutes an initial point in advancing research into hepatotoxicity by shared mechanisms of various substances simultaneously, such as what happened to the patient with the parallel use of Herbalife® and nimesulide.

El hígado es un órgano crucial en el metabolismo y algunas sustancias pueden inducir hepatitis toxica con alta morbimortalidad. La enfermedad hepática inducida por sustancias químicas y medicamentos es un desafío tanto diagnostico como terapéutico, puesto que requiere la realización de estudios de extensión para descartar otras entidades. A continuación se presenta el caso de una paciente femenina de 51 años sin comorbilidades de base, ingresada por clínica de 2 días de evolución consistente en ictericia progresiva, episodios diarreicos sin acolia ni otra manifestación adicional. Aparentemente, su cuadro fue provocado por la administración de nimesulida, 2 tabletas al día por 2 días, contra el dolor secundario a un quiste mandibular diagnosticado en días anteriores. Durante su ingreso a urgencias la paciente describió consumo crónico, a diario desde hace 4 años, de productos de Herbalife®. Cursa con elevación de transaminasas, prolongación del tiempo de protrombina (TP) e hiperbilirrubinemia directa. Se descartan enfermedades infecciosas e inmunológicas. Se decidió iniciar el cubrimiento antibiótico y vitamina K. Finalmente y por exclusión, se realizó una biopsia hepática que sugirió un proceso inflamatorio compatible con hepatitis inducida por fármacos. La mujer evolucionó favorablemente al suspender la medicación y el suplemento dietético referido. En conclusión, el caso expuesto constituye un punto inicial en el avance hacia la investigación en hepatotoxicidad por mecanismos compartidos de diversas sustancias simultáneamente, como lo sucedido a la paciente con el uso paralelo de Herbalife® y de nimesulida.

Formulation and evaluation of Buccal mucoadhesive tablets of diclofenac sodium using 23 factorial designs

Buccal tablets

Diclofenac sodium

Drug release

Mucoadhesion

Mucoadhesive tablets

Release kinetics

Experimental acute anti-inflammatory activity of preparations with complexed cannabidiol in carriers

Abstract Cannabidiol (CBD) is a bioactive compound with promising anti-inflammatory results but has low aqueous solubility. Complexation of drugs with this characteristic in carriers is an alternative to improve their efficiency. This study aimed to prepare and characterize CBD complexes in different carriers, and to evaluate the anti-inflammatory effect of such preparations using an experimental model of edema induction in rat paws. The results were compared to a reference drug, ibuprofen (IBU). The carriers evaluated were beta cyclodextrin (bCD) and activated charcoal (AC). Quantification of the drugs in the complexes was determined, and different qualitative analyses were also performed. Oral treatments in single doses with CBD showed inhibitory effects similar to that of IBU, potentiating its bioactivity without significant adverse effects. CBD*bCD doses at 4.375, 8.75, 17.5, and 35 mg/kg significantly reduced the intensity of edema compared to equivalent doses of pure bioactive. In contrast, CBD*AC did not generate benefits. There was no significant inhibitory effect on myeloperoxidase activity, requiring more specific analyses to assess this parameter. The results suggest that the CBD*bCD complexation is perfectly feasible, increasing its anti-edematogenic efficacy in the experimental model used.

Neuroprotective potential of the Amazonian fruits Euterpe oleracea Mart. and Paullinia cupana Kunth

Abstract Acai (Euterpe oleracea Mart.) and guarana (Paullinia cupana Kunth) are native species from the Amazon Forest that in folk medicine are used to treat several diseases due to their anti-inflammatory and antioxidant properties. This review brings together findings from different studies on the potential neuroprotective effects of acai and guarana, highlighting the importance of the conservation and sustainable exploitation of the Amazon Forest. A bibliographic survey in the PubMed database retrieved indexed articles written in English that focused on the effects of acai and guarana in in vitro and in vivo models of neurodegenerative diseases. In general, treatment with either acai or guarana decreased neuroinflammation, increased antioxidant responses, ameliorated depression, and protected cells from neurotoxicity mediated by aggregated proteins. The results from these studies suggest that flavonoids, anthocyanins, and carotenoids found in both acai and guarana have therapeutic potential not only for neurodegenerative diseases, but also for depressive disorders. In addition, acai and guarana show beneficial effects in slowing down the physiological aging process. However, toxicity and efficacy studies are still needed to guide the formulation of herbal medicines from acai and guarana.

Drimys (cataia, canelo, quiebra-muelas): uma revisão literária sobre sua fitoquímica, atividades biológicas, farmacológicas e toxicológicas / Drimys (cataia, canelo, quiebra-muelas): a literature review on its phytochemistry, biological, pharmacological and toxicological activities / Drimys (cataia, canelo, quiebra-muelas): una revisión bibliográfica sobre sus actividades fitoquímicas, biológicas, farmacológicas y toxicológicas

Drimys é um dos gêneros mais conhecidos da família botânica Winteraceae. As espécies que compõe este gênero têm sido amplamente utilizadas na medicina popular latino americana para o tratamento de malária, dores gástricas, dor de dente, anemia, entre outros. Além do mais, em algumas localidades, as folhas secas e as bagas dos frutos são utilizadas na culinária como condimento pois possuem sabor apimentado. O objetivo deste trabalho foi realizar uma revisão sistemática sobre a fitoquímica, atividades biológicas, farmacológicas e toxicologicas das espécies do gênero Drimys. Para isso, foram realizadas buscas em diferentes plataformas, no período de 1987 e 2022, utilizando-se a palavra "Drimys", indicativa do gênero botânico, acompanhado dos descritores: "Winteraceae", "pharmacology", "neoplasm", "inflammation", "insecticides", "clinical trial", "pain", "food", "ulcer", "malaria" e "toxicity". Incluiu-se trabalhos sobre o perfil fitoquímico, atividades biológicas e potencial farmacológico. Foram selecionados 77 artigos científicos sobre as espécies D. winteri, D. brasiliensis, D. angustifolia, D. granadensis e D. piperita com informações de estudos in vivo e in vitro que possibilitam o conhecimento medicinal, a conservação e o uso sustentável destas espécies.

Drimys is one of the best known genera of the botanical family Winteraceae. The species that make up this genus have been widely used in Latin American popular medicine for the treatment of malaria, gastric pain, toothache, anemia, among others. Moreover, in some places, the dried leaves and berries of the fruits are used in cooking as a condiment because they have a spicy flavor. The objective of this work was to perform a systematic review on the phytochemical, biological, pharmacological and toxicological activities of the species of the genus Drimys. For this, searches were made in different platforms, between 1987 and 2022, using the word "Drimys", indicative of the botanical genus, accompanied by the descriptors: "Winteraceae", "pharmacology", "neoplasm", "inflammation", "insecticides", "clinical trial", "pain", "food", "ulcer", "malaria" and "toxicity". Papers on phytochemical profile, biological activities, and pharmacological potential were included. A total of 77 scientific articles on the species D. winteri, D. brasiliensis, D. angustifolia, D. granadensis and D. piperita were selected, with information from in vivo and in vitro studies that enable medicinal knowledge, conservation and sustainable use of these species.

Drimys es uno de los géneros más conocidos de la familia botánica Winteraceae. Las especies que componen este género han sido ampliamente utilizadas en la medicina popular latinoamericana para el tratamiento de la malaria, dolor gástrico, dolor de muelas, anemia, entre otros. Además, en algunos lugares, las hojas secas y las bayas de los frutos se utilizan en la cocina como condimento porque tienen un sabor picante. El objetivo de este trabajo fue realizar una revisión sistemática sobre las actividades fitoquímicas, biológicas, farmacológicas y toxicológicas de las especies del género Drimys. Para ello, se realizaron búsquedas en diferentes plataformas, entre 1987 y 2022, utilizando la palabra "Drimys", indicativa del género botánico, acompañada de los descriptores: "Winteraceae", "farmacología", "neoplasia", "inflamación", "insecticidas", "ensayo clínico", "dolor", "alimentación", "úlcera", "malaria" y "toxicidad". Se incluyeron artículos sobre perfil fitoquímico, actividades biológicas y potencial farmacológico. Se seleccionaron 77 artículos científicos sobre las especies D. winteri, D. brasiliensis, D. angustifolia, D. granadensis y D. piperita, con información de estudios in vivo e in vitro que permiten el conocimiento medicinal, la conservación y el uso sostenible de estas especies.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents / A Rubiadina exerce um efeito anti-inflamatório agudo e crônico em roedores

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF-α e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1β foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF α e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1β nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents

Abstract: Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF- level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1 level was assessed in the chronic model. One-way ANOVA (post hoc Tukeys) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadins anti-inflammatory effects were associated with a significant IL-1 decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

Resumo A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF- e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1 foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1 nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

Differences of resting-state percent amplitude of fluctuations among migraineurs without aura with different efficacy of non-steroidal anti-inflammatory drugs / 中华行为医学与脑科学杂志

Objective:To explore the differences of resting-state spontaneous neural activity between migraine without aura (MwoA) patients with response or nonresponse to non-steroidal anti-inflammatory drugs (NSAIDs), and its correlation with migraine-related features.Methods:From February 2021 to April 2022, thirty MwoA patients with response to NSAIDs, 30 MwoA patients with nonresponse to NSAIDs, and 30 healthy controls were recruited in the Affiliated Jiangning Hospital of Nanjing Medical University.All subjects were scanned with a 3.0 T resting-state functional magnetic resonance imaging scanner.The percent amplitude of fluctuation (perAF) approach was used to calculate the differences of the resting state brain functional activities among the three groups (Bonferroni multiple comparison correction). SPSS 24.0 software and RESTplus software were used for statistical analysis.Analysis of variance was used for the perAF values of three groups.Correlation analysis was performed between perAF values of brain regions with significant differences and migraine-related features.Results:The brain areas showing significant differences of perAF among the three groups located in the left anterior cingulate cortex (ACC)( x, y, z = -6, 9, -3), left middle frontal gyrus (MFG)( x, y, z =-39, 48, 9) and left middle temporal gyrus (MTG)( x, y, z = -57, -30, -15)(all P<0.05, Bonferroni correction). Compared with nonresponse group, the perAF in response group showed significant decreased in the left ACC, MFG and MTG.There was positive correlation between the perAF of left ACC and disease duration ( r=0.506, P=0.007). Compared with healthy controls, the perAF of nonresponse group showed increased in the left ACC, which was negatively correlated with frequency ( r=-0.414, P=0.032). Conclusion:The neural activity of prefrontal cortex and ACC may be the neuropathological basis underlying response to NSAIDs in MwoA treatment.Moreover, the ACC has certain correlations with migraine-related characteristics, which may serve as a potential neuroimaging biomarker to evaluate the efficacy of NSAIDs.