Myrtus communis leaves: source of bio - actives, traditional use, their biological properties, and prospects / Hojas de Myrtus communis: fuente de bioactivos, uso tradicional, sus propiedades biológicas y perspectivas

Myrtus communis L., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times, the inhabitant s of this area have been using it for its cultural and medicinal properties. Because of the vast diversity of biomolecules in its aerial parts, it exhibits several biological properties, including antioxidant, antimicrobial, and anticancer properties. This review retrospect the research on the source, biological activities with empirical evidence, chemical composition, applications, and cellular targets of extracts and essential oils obtained from M. communis leaves, which provides a perspective for further studies on the applications and formulations of extract and EO of M. communis leaves. The efficacy of constituents' individually, in association with other bioactive constituents, or in combination with available commercial drugs would provide insights in to the development of these bio - actives as future drugs and their evolving future potential applications in the pharmaceutical, food, and aroma industries.

Myrtus communis L., comúnmente conocido como arrayán verdadero, es una planta medicinal originaria de la zona mediterránea. Desde la antigüedad, los habitantes de esta zona lo utilizan por sus propiedades culturales y medicinales. Debido a la gran div ersidad de biomoléculas en sus partes aéreas, exhibe varias propiedades biológicas, incluidas propiedades antioxidantes, antimicrobianas y anticancerígenas. Esta revisión retrospectiva de la investigación sobre la fuente, las actividades biológicas con evi dencia empírica, la composición química, las aplicaciones y los objetivos celulares de los extractos y aceites esenciales obtenidos de las hojas de M. communis , lo que brinda una perspectiva para futuros estudios sobre las aplicaciones y formulaciones de l os extractos y EO de M. communis . La eficacia de los componentes individualmente, en asociación con otros componentes bioactivos o en combinación con medicamentos comerciales disponibles proporcionaría información sobre el desarrollo de estos bioactivos co mo medicamentos futuros y sus futuras aplicaciones potenciales en las industrias farmacéutica, alimentaria y aromática

Função do Ventrículo Direito e Estresse Oxidativo Melhoram com a Administração de Hormônios da Tireoide e Suco de Uva em um Modelo de Hipertensão Pulmonar / Right Ventricular Function and Oxidative Stress Improve with the Administration of Thyroid Hormones and Grape Juice in a Pulmonary Hypertension Model

Resumo Fundamento A remodelação adversa dos vasos pulmonares eleva a pressão pulmonar e provoca hipertensão arterial pulmonar (HAP). A HAP resulta em aumento da pós-carga do ventrículo direito (VD), causando hipertrofia ventricular e consequente insuficiência cardíaca. Não existe um tratamento específico para o remodelamento desadaptativo do VD secundário à HAP. Objetivos Este estudo tem como objetivo explorar duas abordagens terapêuticas, o suco de uva (SU) e os hormônios tireoidianos (HT), no tratamento do estresse oxidativo induzido pela HAP e nas alterações funcionais cardíacas. Métodos Parâmetros ecocardiográficos relacionados à resistência dos vasos pulmonares (relação TA/TE), contratilidade do VD (ESPAT) e função diastólica do VD (relação dos picos E/A) foram avaliados. Além disso, foram medidos ROS totais, peroxidação lipídica, enzimas antioxidantes, proteínas de manipulação de cálcio, expressão de proteínas pró-oxidantes e antioxidantes. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados Ambos os tratamentos, com SU e HT, demonstraram uma redução na resistência pulmonar (~22%), além de melhorias na ESPAT (inotropismo ~11%) e na relação TA/TE (~26%) (p<0,05). Não houve alterações entre os grupos na relação do pico de E/A. Embora ROS e TBARS não tenham sido estatisticamente significativos, os tratamentos com SU e HT diminuíram os níveis de xantina oxidase (~49%) e normalizaram a expressão de HSP70 e proteínas de manipulação de cálcio (p<0,05). No entanto, apenas o tratamento com HT melhorou a função diastólica (~50%) e aumentou o imunoconteúdo de NRF2 (~48%) (p<0,05). Conclusões Até onde sabemos, este estudo é pioneiro ao mostrar que o HT administrado em conjunto com o SU promoveu melhorias funcionais e bioquímicas em um modelo de HAP. Além disso, nossos dados sugerem que os tratamentos com SU e HT se mostraram cardioprotetores, sejam combinados ou não, e exibiram seus benefícios ao modular o estresse oxidativo e as proteínas de manipulação do cálcio.

Abstract Background Adverse remodeling of lung vessels elevates pulmonary pressure and provokes pulmonary arterial hypertension (PAH). PAH results in increased right ventricle (RV) afterload, causing ventricular hypertrophy and the onset of heart failure. There is no specific treatment for maladaptive RV remodeling secondary to PAH. Objectives This study aims to explore two therapeutic approaches, grape juice (GJ) and thyroid hormones (TH), on PAH-induced oxidative stress and cardiac functional changes. Methods Parameters of echocardiography related to lung vessel resistance (AT/ET ratio), RV contractility (TAPSE), and RV diastolic function (E/A peaks ratio) were evaluated. Also, total ROS, lipid peroxidation, antioxidant enzymes, calcium handling proteins, pro-oxidant and antioxidant protein expression were measured. Values of p<0.05 were considered statistically significant. Results Both GJ and TH treatments demonstrated reductions in pulmonary resistance (~22%) and improvements in TAPSE (inotropism ~11%) and AT/ET ratio (~26%) (p<0.05). There were no changes amongst groups regarding the E/A peak ratio. Although ROS and TBARS were not statistically significant, GJ and TH treatments decreased xanthine oxidase (~49%) levels and normalized HSP70 and calcium handling protein expression (p<0.05). However, only TH treatment ameliorated diastolic function (~50%) and augmented NRF2 immunocontent (~48%) (p<0.05). Conclusions To the best of our knowledge, this study stands as a pioneer in showing that TH administered together with GJ promoted functional and biochemical improvements in a PAH model. Moreover, our data suggest that GJ and TH treatments were cardioprotective, combined or not, and exhibited their beneficial effects by modulating oxidative stress and calcium-handling proteins.

Efecto de la fermentación en medio sólido sobre el contenido de fenoles totales y la capacidad antioxidante del maíz / Effect of solid medium fermentation on total phenol content and antioxidant capacity of maize

Resumen: El maíz contiene un gran número de compuestos antioxidantes, muchos de ellos unidos a componentes de la pared celular, por lo que requieren tratamientos para liberarlos, como el uso de enzimas o procesos de fermentación. La fermentación en medio sólido (FMS) con Rhizopus oryzae se ha aplicado para aumentar la capacidad antioxidante (CA) y el contenido fenólico en cereales y leguminosas. El objetivo del presente trabajo fue evaluar el efecto de la FMS con R. oryzae sobre la CA y el contenido de fenoles totales (CFT) del maíz. La FMS se realizó en bolsas zip-lock (25 cm2) a 30 °C/72 h, con un inóculo de 1 x 106 esporas/g. Se tomaron muestras cada 12 h, el extracto se recuperó con etanol al 80 % y se utilizó para determinar el CFT y la CA (ensayo ABTS+, DPPH y FRAP). Los valores más altos se obtuvieron a las 60 h de cultivo, con un CFT de 1.92 mg/ gramos de materia seca (gms) y una CA de 1.47 mg de equivalentes Trolox por gramo de materia seca (mg ET/gms), 1.27 mg ET/gms y 5.8 mg Fe+2/gms para los ensayos de ABTS+, DPPH y FRAP, respectivamente. El uso de FMS permitió aumentar hasta 0.83 y 1.25 veces el CFT y la CA del maíz, con respecto al tiempo 0 h. El maíz fermentado con R. oryzae mostró potencial para ser empleado como materia prima para el desarrollo de alimentos funciona les, al incrementar su CA a través de un bioproceso.

Abstract: Maize contains a large number of antioxidant compounds. However, many of them are not in free form, as they are bound to components of the cell wall of maize kernels. For this reason, the use of treatments is required to release them, such as the use of enzymes or fermentation processes. Fermentation in solid medium (FMS) with Rhizopus oryzae has been applied to increase the antioxidant capacity (AC) and phenolic content in cereals and legumes. The objective of the present work was to evaluate the effect of FMS with R. oryzae on AC and total phenolic content (TPC) of maize. Fermentation on solid medium was carried out in zip-lock bags (25 cm2) at 30 °C for 72 h, with an inoculum of 1 x 106 spores/g. Samples were taken every 12 h, the extract was recovered with 80% ethanol, and used to determine TPC and AC (ABTS+, DPPH and FRAP essay). The highest values were obtained at 60 h of culture, with a TPC of 1.92 mg/gram dry metter (gdm) and an AC of 1.47 mg TE/gmd, 1.27 mg TE/gdm and 5.8 mg Fe+2/gdm for the ABTS+, DPPH and FRAP assays, respectively. The use of FMS allowed to increase up to 0.83 and 1.25 times the CFT and CA of corn, with respect to time zero. Corn fermented with R. oryzae showed potential to be used as a raw material for the development of functional foods, by increase its AC through a bioprocess.

Influencia del consumo de hidratos de carbono sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional / Influence of carbohydrate intake on oxidative status among women with and without gestational diabetes mellitus

RESUMEN Objetivo: Identificar la influencia del consumo de hidratos de carbono (HCO) sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional (DMG). Materiales y métodos: Se realizó un estudio transversal, observacional y comparativo a dos grupos de 21 mujeres con y sin DMG, respectivamente, en la ciudad de Toluca, México, de enero a diciembre del 2022. Para evaluar parámetros sociodemográficos, se les aplicó un cuestionario de historia clínica; en cuanto a los parámetros antropométricos, se les midió peso corporal y estatura; y respecto a los parámetros bioquímicos, colesterol total (CT) y triglicéridos (TG). Para evaluar el estado oxidante/antioxidante se cuantificaron, como marcador oxidante, el malondihaldeído (MDA), y como antioxidantes, catalasa (cat), superóxido dismutasa (SOD) y capacidad antioxidante total (CAT). Los hábitos dietéticos se evaluaron a través de un recordatorio de 24 horas, en ambos grupos de mujeres, para obtener los macronutrientes: proteínas, lípidos e HCO. A partir de los hidratos de carbono totales (HCOT), se calcularon los hidratos de carbono complejos (HCOC) e hidratos de carbono simples (HCOS) como la sacarosa. Para el cálculo de HCOS por día, se usó la lista de alimentos con contenido de sacarosa por cada 100 gramos de consumo que emplea el Sistema Mexicano de Equivalentes; para el análisis de dieta, se utilizó el programa Nutrikcal VO. Se usaron las pruebas estadísticas t de Student para muestras independientes, U de Mann-Whitney para las variables no homogéneas y se realizó la correlación de Spearman (p < 0,05) en el programa SPSS, versión 19. Resultados: Los resultados mostraron que la diferencia entre los valores de CT (p < 0,029), TG (p < 0,029), las enzimas: cat (p < 0,011), SOD (p < 0,013), así como el MDA (p < 0,039), fueron significativamente mayores en las pacientes del grupo con DMG en comparación con el grupo sin DMG. Además, el grupo con DMG consumió mayor proporción de sacarosa. Conclusiones: Las mujeres con DMG tienen un desequilibrio en el estado oxidante/antioxidante influenciado por el tipo de HCO que consumen, en particular los HCOS como la sacarosa.

ABSTRACT Objective: To identify the influence of carbohydrate (CHO) intake on oxidative status among women with and without gestational diabetes mellitus (GDM). Materials and methods: A cross-sectional, observational and comparative study was carried out with two groups of 21 women each with and without GDM in the city of Toluca, Mexico, from January to December 2022. The sociodemographic parameters were determined by administering the patients a medical history questionnaire; anthropometric parameters such as body weight and height were measured; and biochemical parameters including total cholesterol (TC) and triglycerides (TG) were calculated. The oxidant/antioxidant status was assessed as follows: malondialdehyde (MDA) as oxidative stress marker; and catalase (CAT), superoxide dismutase (SOD) and total antioxidant capacity (TAC) as antioxidants. Dietary habits were evaluated through a 24-hour reminder in both groups of women to obtain the macronutrient classes, i.e., proteins, fats and CHOs. Based on the total carbohydrates (TCHOs), complex (CCHOs) and simple carbohydrates (SCHOs) such as sucrose were calculated. SCHOs per day were measured using the list of foods with sucrose content per 100 grams according to the Mexican Food Equivalence System (SMAE). The NutriKcal VO program was used for the dietary analysis. Statistical tests such as Student's t test and Mann-Whitney U test were performed for the independent samples and nonhomogeneous variables, respectively, and Spearman's rank correlation coefficient (p < 0.05) was determined using the IBM SPSS Statistics V19. Results: The results showed that the difference between the levels of TC (p < 0.029), TG (p < 0.029), enzymes CAT (p < 0.011) and SOD (p < 0.013), as well as MDA (p < 0.039) was significantly higher among patients in the group with GDM compared to that in the group without GDM. In addition, the group with GDM consumed a higher proportion of sucrose. Conclusions: Women with GDM have an imbalance in the oxidant/antioxidant status, influenced by the type of CHO they consume, particularly SCHOs such as sucrose.

Antioxidative responses of Melon Manis Terengganu (MMT) against Fusarium sp

Aims@#Melon Manis Terengganu, MMT is one of the economically important fruits in Terengganu, which contains numerous nutritional values and bioactive compounds that benefit human health. The major problem is MMT has been affected by Fusarium sp., which is the common fungus in the Cucurbitaceae family resulting in Fusarium wilt disease and lowering melon production. It may also affect the antioxidant value of MMT; however, limited study has been conducted on this issue. Hence, the objective of this study was to determine the non-enzymatic as well as enzymatic activities in response to Fusarium sp. (S2 and S4) infection. @*Methodology and results@#In this study, MMT leaves were incubated in culture filtrate (CF) obtained from Murashige and Skoog (MS) liquid medium. The antioxidative responses were assayed at 0, 1, 3, 5, 7 and 9 days of treatment. In response to Fusarium infection, the ascorbic acid, α-tocopherol and carotenoid content were significantly stimulated at the early stages of the experiment and slowly reduced afterward. This current study also demonstrated that the CAT-specific activities were initially induced in S2 CF-treated leaves. Similar APX and gPOD specific activity patterns were observed in both S2 and S4 CFs treatments. The APX and gPOD-specific activities were induced at the later stages of infection in S4 CF-treated leaves. @*Conclusion, significance and impact of study: @#The results revealed that enzymatic and non-enzymatic antioxidants worked together to fight against stress caused by the fungal infection, with the activation of the plant defense system.

Antioxidant effect of Rosa pimpinellifolia L. fruit extract on cholestatic liver injury: an experimental study

SUMMARY BACKGROUND: Antioxidants have been considered a rational curative strategy to prevent and cure liver diseases involving oxidative stress. An acute obstructive jaundice rat model was established to investigate the in vivo hepatoprotective efficacy of Rosa pimpinellifolia L. METHODS: The experimental jaundice model was performed by binding the main bile duct in 25 male Sprague-Dawley rats. All rats were randomly divided into five groups: first group: laparotomy-sham-only, second group: biliary tract binding (control), and third, fourth, and fifth groups: treatment groups with 250, 500, and 750 mg/kg fruit extracts daily, respectively. RESULTS: Considering dosage, although there was no significant therapeutic effect in the 250 mg/kg of Rosa pimpinellifolia L. group, the best results were found in the 500 mg/kg dose group, while results in the 750 mg/kg dose group showed consistent correlation with proinflammatory response. With regard to biochemical parameters, lipid hydroperoxide level in the rat serum and liver tissue was significantly decreased in all treatment groups. Amadori products, which are one of the early markers of glycol-oxidative stress, showed statistical significance in the treatment. CONCLUSION: It was revealed that the antioxidant effect of Rosa pimpinellifolia L. was more prominent in the early stages of hepatic injury secondary to oxidative stress.

Synthesis and evaluation of 2-phenylamino-1, 4-naphthoquinones derivatives as potential hypoglycaemic agents / Síntese e avaliação de derivados de 2-fenilamino-1, 4-naftoquinonas como potenciais agentes hipoglicemiantes

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents

Abstract Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of chloro group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Resumo Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo cloro tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Effects of rosmarinic acid and doxorubicine on an ovarian adenocarsinoma cell line (OVCAR3) via the EGFR pathway

Purpose: We aimed to reveal the effects of rosmarinic acid (RA), which has come to the forefront with its antitumor and antioxidant properties in many studies recently in the ovarian adenocarcinoma cell line, on the epidermal growth factor receptor (EFGR) signaling pathway in the presence of doxorubicin (DOX). Methods: Ovarian adenocarcinoma cell line (OVCAR3) and human skin keratinocyte cell line human skin keratinocyte cell line (HaCaT) were used as control. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied to determine the effect of RA and DOX on the proliferation of OVCAR3 and HaCaT cells. Bcl2 expression and epidermal growth factor receptor (EGFR) and western blot analysis were performed to determine the expression levels of the markers. Results: It was determined that RA (IC50 = 437.6 µM) and DOX (IC50 = 0.08 µM) have the ability to inhibit the proliferation of OVCAR3 cells and induce apoptosis in a 72-hour time and dose-dependent manner. Western blot showed that the expression level of Bcl-2 and EGFR in OVCAR3 cells was down-regulated by RA and DOX. Conclusions: Apoptosis in OVCAR3 cells can potentially be induced by RA via the EGFR pathway, and RA may be a potent agent for cancer therapy.

Bone protective effect of sinomenine against monosodium iodoacetate induced knee and hip injury in rat model: an inflammatory pathway

Purpose: Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. Methods: MIA (3 mg/50 µL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Results: Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Conclusions: Sinomenine is a beneficial active agent for the treatment of OA disease.

Ellagic acid protected the gingival tissue via fibroblast and epidermal growth factors in rats

Purpose: To investigate the effect of ellagic acid (EA) in gingival tissues injury in rats. Methods: Twenty rats were categorized into two groups. In burn group, an excisional wound area was created by removing a 4-mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In burn + ellagic acid group, 1.2 mg/mL EA was administered as irrigation for one week. Animals was sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) level were measured. Hematoxylin and eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostainings were applied to tissues. Results: MDA, MPO, inflammation and leukocyte infiltration were high in burn group. Degeneration epithelium, edema and inflammatory cell infiltration in connective tissue areas, and dilatation and congestion in blood vessels were observed in burn group. In burn + EA group, the gingival epithelium improved, collagen fiber production increased and organized dermis were observed. After burn injury, FGF and EGF activity was increased in EA treated groups. Conclusions: We suggest that EA have the potential for better healing outcomes in oral wounds. EA seems to have promising therapeutic efficacy to enhance oral wound healing.

Glutathione effect on functional and histological recovery after spinal cord injury in rats

Abstract Objective The aim of this study was to evaluate the GSH effect on functional and histological recovery after experimental spinal cord injury in rats. Methods Forty Wistar rats were subjected to spinal cord injury through the Multicenter Animal Spinal Cord Injury Study (MASCIS) Impactor system. The rats were sorted and divided into four groups, as follows: Group 1 ‒ Laminectomy and spinal cord injury; Group 2 ‒ Laminectomy, spinal cord injury and Saline Solution (SS) 0.9%; Group 3 ‒ Laminectomy, spinal cord injury, and GSH; and Group 4 ‒ lLaminectomy without spinal cord injury. GSH and SS were administered intraperitoneally. Groups 1 and 4 received no intervention. Results The rats were evaluated for locomotor function recovery at seven different times by the Basso, Beattie, and Bresnahan (BBB) scale on days 2, 7, 14, 21, 28, 35, and 42 after the spinal cord injury. On day 42, the rats were sacrificed to analyze the histological findings of the injured spinal cord. In the group submitted to GSH, our experimental study revealed better functional scores on the BBB scale, horizontal ladder scale, and cranial and caudal axon count. The differences found were statistically significant in BBB scores and axonal count analysis. Conclusion This study demonstrated that using glutathione in experimental spinal trauma can lead to better functional recovery and improved axonal regeneration rate in Wistar rats submitted to experimental spinal cord injury.

Color stability of enamel treated with different antioxidant agents following at-home bleaching with 10% hydrogen peroxide

Abstract Objective This study evaluated the color stability of enamel submitted to 10% hydrogen peroxide (HP) followed by antioxidants agents, and the pH and antioxidant activity (AA%) of these agents. Methodology Bovine enamel-dentin blocks were randomly distributed into groups (n=10/group): GNC (negative control: no treatment); GPC (positive control: bleaching only); TOC_10% (HP+10% α-tocopherol); GT_10% (HP+10% green tea extract); GS_5% (HP+5% grape seed extract); SA_10% (HP+10% sodium ascorbate); QUI_10% (HP+10% quinoa extract); and QC_1% (HP+1% quercetin). Color (ΔE00) and whiteness index (ΔWID) changes were analyzed using a digital spectrophotometer. The pH and AA% were determined using a pH meter and the DPPH method, respectively. Data were analyzed by ANOVA/Tukey's and Dunnett's tests (α=0.05). Results At 14 days post-bleaching, GNC promoted the lowest ΔWID and ΔE00 (p<0.05), and no differences were found between GPC and the remaining groups submitted to the antioxidant agents (p>0.05). QC_1% and QUI_10% exhibited acidic pH levels (3.64 and 4.75, respectively), whereas TOC_10% and GS_5% exhibited alkaline pH (7.07 and 7.64, respectively). No differences in AA% were found between the agents (p>0.05), ranging from 92.6 to 97.6%. Conclusion The antioxidant agents did not interfere in bleached enamel color stability, showing satisfactory antioxidant activity. However, QUI and QC gels displayed acidic pH. Clinical significance: The antioxidants evaluated showed high AA% and no impact on post-bleaching color stability, suggesting that their capacity to recover bond strength demonstrated elsewhere would not compromise the esthetic efficacy of tooth bleaching. However, those with acidic pH should be used with caution due to potential enamel damage.

Is there a difference in the oxidative stress levels between type 2 diabetic individuals with and without periodontitis? Systematic review / Existe diferença nos níveis de estresse oxidativo entre indivíduos com diabetes tipo 2 com e sem periodontite? Revisão Sistemática

Objective: The authors' aim in this systematic review was to verify the scientific evidence for difference of oxidative stress biomarkers in individuals with type 2 diabetes mellitus with and without periodontitis. Material and Methods: Observational studies, baseline data of prospective and interventional studies were searched on the following databases: Virtual Health Library, Web of Science, PubMed, Embase, Scopus, Cochrane Library, Opengrey and Google Scholar. The electronic search was performed in June 01, 2020 until May 17, 2024 with alerts until June 01, 2024. The quality assessment and the certainty of the evidence of the included studies were evaluated through Fowkes and Fulton's checklist and GRADEpro Guideline Development Tool. Results: Of 988 relevant articles, the authors included 9 studies for the final analysis. Among those studies, 4 cross-sectional, 3 case-control, and 2 interventional studies were included. The analysis of non-randomized clinical trials properly reported most of the criteria analyzed in Summary questions (Bias, Confounding and Chance) as present in 3 studies. In six studies confounding factors were no detected. Due to the variation in the study results and clinical/methodological heterogeneity, a meta-analysis was not appropriate. The studies reported high concentrations of oxidizing agents and low antioxidants levels in individuals with type 2 diabetes mellitus and periodontitis when compared to with no periodontitis. Conclusion: Considering the few studies found, the methodological flaws, few markers studied and absence homogeneity in the evaluation of redox balance markers, as well as, the very low certainty of the evidence among included studies, it was not possible to determine whether there are or not differences in the oxidative stress levels in individuals with type 2 diabetes with and without periodontitis, and therefore, further prospective observational and interventional studies are recommended. (AU)

Objetivo: O objetivo dos autores nesta revisão sistemática foi verificar a evidência científica para a diferença de biomarcadores de estresse oxidativo em indivíduos com diabetes mellitus tipo 2 com e sem periodontite. Material e Métodos: estudos observacionais, dados de base de estudos prospectivos e intervencionistas foram pesquisados nas seguintes bases de dados: Biblioteca Virtual em Saúde, Web of Science, PubMed, Embase, Scopus, Cochrane Library, Opengrey e Google Scholar. A busca eletrônica foi realizada no período de 01 de junho de 2020 até 17 de maio de 2024, com alertas até 01 de junho de 2024. A avaliação da qualidade e a certeza da evidência dos estudos incluídos foi realizada através da lista de checagem Fowkes and Fulton's e da Ferramenta de desenvolvimento de diretrizes GRADEpro. Resultados: Dos 988 artigos relevantes, os autores incluíram 9 estudos para a análise final. Entre esses estudos, foram incluídos 4 estudos transversais, 3 de caso-controle e 2 de intervenção. A análise dos ensaios clínicos não randomizados relatou adequadamente a maioria dos critérios analisados nas questões resumo (Viés, Confundimento e Resultados ao caso) presentes em 3 estudos. Fatores de confusão não foram detectados em seis estudos. Devido à variação nos resultados do estudo e à heterogeneidade clínica/metodológica, não foi possível realizar uma meta-análise. Os estudos relataram altas concentrações de agentes oxidantes e baixos níveis de antioxidantes em indivíduos com diabetes mellitus tipo 2 e periodontite quando comparados a indivíduos sem periodontite. Conclusão: Considerando os poucos estudos encontrados, as falhas metodológicas, poucos marcadores estudados e ausência de homogeneidade na avaliação dos marcadores do balanço redox, bem como a baixíssima certeza da evidência entre os estudos incluídos, não foi possível determinar se há diferenças nos níveis de estresse oxidativo em indivíduos com diabetes tipo 2 associado e não à periodontite e, portanto, outras observações prospectivas e estudos de intervenção são recomendados (AU)

Investigation of crude methanolic extract from poison secreted by the Rhaebo gutattus on status redox antioxidant in mice

The study evaluated the antioxidant properties of a crude methanolic extract (CME) from Rhaebo guttatus poison in mice over a period of 7 and 30 days. The mice were divided into groups and treated with different concentrations of the extract (0; 8 µg mL-1; 16 µg mL-1 and 32 µg mL-1 or vehicle; 100 µL/animal/day; via gavage). The liver samples were analyzed for status redox parameters as catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). The results showed that the CME caused changes in the levels of various antioxidants and oxidative stress markers. At 7 days, there was an increase in TBARS levels (8 µg mL-1 dose) and GST activity (16 µg mL-1 dose), and a reduction in GSH levels (32 µg mL-1 dose) compared to the control group. At 30 days, TBARS and GSH levels returned to control values in the same period, but GSH increased (32 µg mL-1 dose) compared at 7 days; GST activity remained high after 30 days for 32 µg mL-1 dose compared other groups and time of treatment (7 days). Overall, the study suggests that the extract modulates antioxidant properties per se that can affect various markers of status redox in the liver of mice, mainly 16 µg mL-1 dose demonstrated to act under antioxidant enzymes in different times (7 or 30 days).

The impact of COVID-19 on vitamin E concentrations and oxidative stress markers in adult subjects: A systematic review

Objective: To determine the impact of COVID-19 on vitamin E concentrations and oxidative stress in patients affected by the disease. Method: We conducted a systematic review using observational studies published between 2020 and 2023, which addressed the impact of COVID-19 on vitamin E concentrations and oxidative stress in patients affected by the disease. Review articles, clinical trials, letters to the editor, as well as studies conducted with pregnant women, animals and/or in vitro tests, and in languages other than English were excluded from this search. Studies were selected through a literature search in the following electronic databases: PubMed, Science Direct, and Web of Science, from October 2022 to May 2023. Results: Three articles were included in this review, consisting of patients with mild to severe symptoms, including those hospitalized in the intensive care unit. The reduction in vitamin E concentrations was in all studies accompanied by a reduction in enzymes involved in antioxidant action, such as superoxide dismutase, glutathione peroxidase, and glutathione reductase. In parallel to this, studies showed elevated concentrations of lipid peroxidation markers, such as malondialdehyde and myeloperoxidase. Conclusion: Infection with the SARS-COV-2 alters the activity of antioxidant cells and free radical defense agents.

Objetivo: Determinar el impacto del COVID-19 sobre las concentraciones de vitamina E y el estrés oxidativo en pacientes afectados por la enfermedad. Método: Se trata de una Revisión Sistemática, realizada mediante una prospección de estudios observatorios publicados entre 2020 y 2023, que abordaron el impacto de la COVID-19 sobre las concentraciones de vitamina E y el estrés oxidativo en pacientes afectados por la enfermedad. Se excluyeron de esta búsqueda artículos de revisión, ensayos clínicos, cartas al editor, así como estudios realizados con mujeres embarazadas, animales y/o ensayos in vitro, y en idiomas distintos al inglés. Los estudios se seleccionaron mediante una búsqueda bibliográfica en las siguientes bases de datos electrónicas: PubMed, Science Direct y Web of Science, desde octubre de 2022 hasta mayo de 2023. Resultados: Se incluyeron tres artículos en esta revisión, que consistían en pacientes con síntomas de leves a graves, incluidos los hospitalizados en la unidad de terapia intensiva. La reducción de las concentraciones de vitamina E se acompañó en todos los estudios de una reducción de las enzimas implicadas en la acción antioxidante, como la superóxido dismutasa, la glutatión peroxidasa y la glutatión reductasa. Paralelamente, los estudios mostraron concentraciones elevadas de marcadores de peroxidación lipídica, como el malondialdehído y la mieloperoxidasa. Conclusiones: La infección por el virus del SARS-CoV-2 altera la actividad de las células antioxidantes y de los agentes de defensa contra los radicales libres.

Comparación potencial de las actividades antiinflamatorias de las formulaciones de enjuague bucal de quercetina y diclofenaco / 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)

Flavonoides como suplementos para mejorar el rendimiento físico deportivo / Flavonoids as Supplements to Improve Sports Physical Performance

Introducción: El ejercicio físico puede generar especies reactivas de oxígeno que dañan componentes celulares esenciales, como la fatiga. Los flavonoides, debido a su baja toxicidad y actividad antioxidante, se han estudiado como potenciales suplementos alimenticios para mejorar el rendimiento deportivo. Objetivo: Describir la evidencia científica que se ha obtenido sobre la eficacia del uso de flavonoides como suplementos para mejorar el rendimiento físico deportivo. Métodos: Se realizó una búsqueda sobre la eficacia del uso de flavonoides como suplementos para el rendimiento físico y deportivo en las bases de datos PubMed y Google Scholar. Se utilizaron las palabras clave: flavonoid, supplementation, sport, exercise, fatigue, muscle, fats, physical activity, y se tomaron en cuenta los artículos publicados entre los años 2018 y 2022, en idioma inglés que cumplieron con los criterios de selección. Resultados: Los flavonoides son capaces de disminuir la fatiga debido al esfuerzo físico en un contexto deportivo, principalmente debido a su capacidad de regular la actividad de agentes antioxidantes endógenos como las enzimas superóxido dismutasa, catalasa y glutatión peroxidasa, que se encargan de la neutralización de las especies reactivas de oxígeno. Además, son capaces de favorecer la neutralización de metabolitos tóxicos que se generan durante el ejercicio y de aumentar las reservas energéticas (glicógeno en el hígado y músculos) y la resistencia muscular. Conclusiones: Existe evidencia científica de que los flavonoides son capaces de mejorar el rendimiento físico deportivo principalmente al disminuir la fatiga e incrementar la resistencia muscular(AU)

Introduction: Physical exercise can generate reactive oxygen species that damage essential cellular components, such as fatigue. Flavonoids, due to their low toxicity and antioxidant activity, have been studied as potential dietary supplements to improve sports performance. Objective: To describe the scientific evidence that has been obtained on the efficacy of the use of flavonoids as supplements to improve sports physical performance. Methods: A search was carried out, in PubMed and Google Scholar databases, on the efficacy of the use of flavonoids as supplements for physical and sports performance. The keywords were used flavonoid, supplementation, sport, exercise, fatigue, muscle, fats, physical activity. Articles published from 2018 to 2022, in English, that met the selection criteria were taken into account. Results: Flavonoids are capable of reducing fatigue due to physical exertion in a sports context, mainly due to their ability to regulate the activity of endogenous antioxidant agents such as superoxide dismutase, catalase and glutathione peroxidase enzymes, which are responsible for the neutralization of reactive oxygen species. In addition, they are capable of favoring the neutralization of toxic metabolites that are generated during exercise and of increasing energy reserves (glycogen in the liver and muscles) and muscular resistance. Conclusions: There is scientific evidence that flavonoids are capable of improving sports physical performance, mainly by reducing fatigue and increasing muscular resistance(AU)

Antioxidant rich medicinal plants as a potential candidate to treat gastric ulcer / Plantas medicinales ricas en antioxidantes como candidatas potenciales para tratar la úlcera gástrica

Oxidative stress is a key cause of gastrointestinal disorders, primarily stomach ulcers. Multiple intrinsic and extrinsic mechanisms caused the body to produce reactive oxygen species (ROS). The body's antioxidant defense system protects against these reactive species. When the degree of ROS production exceeds the normal range, the body's natural defense system fails to neutralize these dangerous free radicals, necessitating need for an exogenous source of natural antioxidants. Natural herbal remedies have been widely employed as antioxidants to relieve oxidative stress in gastric ulcers. Polyphenols, tannins, essential oils, flavonoids, notably quercetin, carotenoids, vitamin C, vitamin A, and minerals are among the molecules of immense interest in bioassays due to their significant antioxidant effects. In the present review, several natural anti-ulcer medicinal plants along with their antioxidative mechanism have been reported. Electronic databases including PubMed, Google Scholar and Scopus were explored to identify the antioxidant and gastroprotective potential of all the plants.

El estrés oxidativo es una causa clave de trastornos gastrointestinales, principalmente úlceras estomacales. Múltiples mecanismos intrínsecos y extrínsecos hacen que el cuerpo produzca especies reactivas de oxígeno (ROS). El sistema de defensa antioxidante del cuerpo protege contra estas especies reactivas. Cuando el grado de producción de ROS excede el rango normal, el sistema de defensa natural del cuerpo no logra neutralizar estos peligrosos radicales libres, lo que requiere de una fuente exógena de antioxidantes naturales. Los remedios herbales naturales se han empleado ampliamente como antioxidantes para aliviar el estrés oxidativo en las úlceras gástricas. Los polifenoles, los taninos, los aceites esenciales, los flavonoides, en particular la quercetina, los carotenoides, la vitamina C, la vitamina A y los minerales se encuentran entre las moléculas de mayor interés en los bioensayos debido a sus importantes efectos antioxidantes. En la presente revisión se han reportado varias plantas medicinales naturales antiulcerosas junto con su mecanismo antioxidante. Se exploraron bases de datos electrónicas como PubMed, Google Scholar y Scopus para identificar el potencial antioxidante y gastroprotector de todas las plantas.