Quercetin Inhibits IL-1β-Induced Inflammation, Hyaluronan Production and Adipogenesis in Orbital Fibroblasts from Graves' Orbitopathy

Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed. We investigated the effect of quercetin in primary cultured orbital fibroblasts from GO, targeting pathways of inflammation, aberrant accumulation of extracellular matrix macromolecules, and adipose tissue expansion. Quercetin significantly attenuated intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and cyclooxygenase (COX) -2 mRNA expression, and inhibited IL-1β-induced increases in ICAM-1, IL-6, and IL-8 mRNA. Increased hyaluronan production induced by IL-1β or tumor necrosis factor-α was suppressed by quercetin in a dose- and time-dependent manner. Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and C/EBPβ proteins. In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO

Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role

Chelation Therapy with Desferrioxamine does not Normalize Ferritin Level but Attenuates Oxidative Damage and Improves Total Antioxidant Level in Malaysian Chinese β-thalassaemia Major Patients

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in β-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxamine-chelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients’ PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese b-thalassaemia major patients. Keywords: Beta-thalassaemia major, desferrioxamine, Malaysian Chinese, non-chelated, oxidative stress La Terapia de Quelación con Deferoxamina no Normaliza los Niveles de Ferritinaa pero Atenúa el daño Oxidativo y Mejora el Nivel Antioxidante Total en los Pacientes Sinomalayos que Padecen de Talasemia ß RESUMEN La beta-talasemia mayor causa anemia severa, y los pacientes con este padecimiento pueden hacerse dependientes de las transfusiones de sangre por el resto de sus vidas. Las transfusiones regulares de sangre dan lugar a una sobrecarga de hierro que conduce al daño oxidativo, el cual a su vez puede acelerar la mortalidad. El objetivo de esta investigación fue estudiar las tasas de oxidantes-antioxidantes en pacientes de beta-talasemia mayor en el Centro Médico de la Universidad de Malaya, tanto aquellos bajo tratamiento de quelación con deferoxamina, como aquellos sin terapia de quelación alguna. Se recogieron muestras de sangre de 39 pacientes chinos y 20 controles. Se extrajeron plasma y lisados de células mononucleares periféricas (CMSP), y se realizaron pruebas bioquímicas para evaluar el estrés oxidativo. El estrés oxidativo era evidente en estos pacientes en forma de productos avanzados de oxidación de proteínas (PAOP), y los hidroperóxidos de lípidos eran elevados, en tanto que la actividad de glutatión peroxidasa y el poder reductor férrico/antioxidante (FRAP) era reducida. La actividad de la catalasa en los pacientes de CMSP era elevada, posiblemente como un mecanismo compensatorio frente a la actividad de glutatión peroxidasa reducida tanto en los glóbulos rojos como en las CMSP. Los niveles más bajos de FRAP y los más altos de PAOP en los pacientes no quelados en comparación con los pacientes quelados, indicaban un bajo nivel de estrés oxidativo en los pacientes quelados. Los niveles de ferritina tanto en los pacientes quelados como en los no quelados, eran altos, y los niveles promedio de actividades enzimáticas del hígado fueron elevados en la mayoría de los pacientes, independientemente de la terapia de quelación. En conclusión, este estudio indica que la terapia de quelación con deferoxamina no normaliza el nivel de ferritina, pero en cambio atenúa el daño oxidativo, y mejora el nivel antioxidante total en los pacientes sinomalayos afectados por la beta-talasemia mayor. Keywords: Beta-thalassaemia major, desferrioxamine, Malaysian Chinese, non-chelated, oxidative stres

Chelation Therapy with Desferrioxamine does not Normalize Ferritin Level but Attenuates Oxidative Damage and Improves Total Antioxidant Level in Malaysian Chinese β-thalassaemia Major Patients

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in β-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxamine-chelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients’ PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese b-thalassaemia major patients. Keywords: Beta-thalassaemia major, desferrioxamine, Malaysian Chinese, non-chelated, oxidative stress La Terapia de Quelación con Deferoxamina no Normaliza los Niveles de Ferritinaa pero Atenúa el daño Oxidativo y Mejora el Nivel Antioxidante Total en los Pacientes Sinomalayos que Padecen de Talasemia ß RESUMEN La beta-talasemia mayor causa anemia severa, y los pacientes con este padecimiento pueden hacerse dependientes de las transfusiones de sangre por el resto de sus vidas. Las transfusiones regulares de sangre dan lugar a una sobrecarga de hierro que conduce al daño oxidativo, el cual a su vez puede acelerar la mortalidad. El objetivo de esta investigación fue estudiar las tasas de oxidantes-antioxidantes en pacientes de beta-talasemia mayor en el Centro Médico de la Universidad de Malaya, tanto aquellos bajo tratamiento de quelación con deferoxamina, como aquellos sin terapia de quelación alguna. Se recogieron muestras de sangre de 39 pacientes chinos y 20 controles. Se extrajeron plasma y lisados de células mononucleares periféricas (CMSP), y se realizaron pruebas bioquímicas para evaluar el estrés oxidativo. El estrés oxidativo era evidente en estos pacientes en forma de productos avanzados de oxidación de proteínas (PAOP), y los hidroperóxidos de lípidos eran elevados, en tanto que la actividad de glutatión peroxidasa y el poder reductor férrico/antioxidante (FRAP) era reducida. La actividad de la catalasa en los pacientes de CMSP era elevada, posiblemente como un mecanismo compensatorio frente a la actividad de glutatión peroxidasa reducida tanto en los glóbulos rojos como en las CMSP. Los niveles más bajos de FRAP y los más altos de PAOP en los pacientes no quelados en comparación con los pacientes quelados, indicaban un bajo nivel de estrés oxidativo en los pacientes quelados. Los niveles de ferritina tanto en los pacientes quelados como en los no quelados, eran altos, y los niveles promedio de actividades enzimáticas del hígado fueron elevados en la mayoría de los pacientes, independientemente de la terapia de quelación. En conclusión, este estudio indica que la terapia de quelación con deferoxamina no normaliza el nivel de ferritina, pero en cambio atenúa el daño oxidativo, y mejora el nivel antioxidante total en los pacientes sinomalayos afectados por la beta-talasemia mayor. Keywords: Beta-thalassaemia major, desferrioxamine, Malaysian Chinese, non-chelated, oxidative stres

Protective Effect of Carica papaya L Leaf Extract against Alcohol Induced Acute Gastric Damage and Blood Oxidative Stress in Rats

ABSTRACT The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress. "Efecto Protectivo del Extracto de la Hoja de Carica papaya L Contra el Daño Gástrico Agudo Inducido por Alcohol y el Estrés Oxidativo en Ratas" RESUMEN Los efectos de; extracto acuoso de la hoja de Carica papaya (CPL) en el daño gástrico agudo inducido por alcohol y el nivel de estrés oxidativo inmediato en la sangre, fueron estudiados en ratas. Los resultados mostraron que el índice de úlcera gástrica se reducía significativamente en ratas pretratadas con extracto de CPL, en comparación con los controles tratados con alcohol. Los estudios in vitro mediante el ensayo con 2,2-difenil-1-picrihidrazilo) mostraron la fuerte naturaleza antioxidante de extracto de CPL. El análisis bioquímico indicó que el daño agudo inducido por alcohol se refleja en las alteraciones de los índices oxidativos de la sangre y el extracto de CPL ofreció cierta protección con la reducción del nivel de peroxidación lipídica del plasma y el aumento de la actividad de la glutatión peroxidasa de los eritrocitos. La hoja de la Carica papaya puede servir potencialmente como un buen agente terapéutico para la protección contra la úlcera gástrica y el estrés oxidativo

Protective Effect of Carica papaya L Leaf Extract against Alcohol Induced Acute Gastric Damage and Blood Oxidative Stress in Rats

ABSTRACT The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress. "Efecto Protectivo del Extracto de la Hoja de Carica papaya L Contra el Daño Gástrico Agudo Inducido por Alcohol y el Estrés Oxidativo en Ratas" RESUMEN Los efectos de; extracto acuoso de la hoja de Carica papaya (CPL) en el daño gástrico agudo inducido por alcohol y el nivel de estrés oxidativo inmediato en la sangre, fueron estudiados en ratas. Los resultados mostraron que el índice de úlcera gástrica se reducía significativamente en ratas pretratadas con extracto de CPL, en comparación con los controles tratados con alcohol. Los estudios in vitro mediante el ensayo con 2,2-difenil-1-picrihidrazilo) mostraron la fuerte naturaleza antioxidante de extracto de CPL. El análisis bioquímico indicó que el daño agudo inducido por alcohol se refleja en las alteraciones de los índices oxidativos de la sangre y el extracto de CPL ofreció cierta protección con la reducción del nivel de peroxidación lipídica del plasma y el aumento de la actividad de la glutatión peroxidasa de los eritrocitos. La hoja de la Carica papaya puede servir potencialmente como un buen agente terapéutico para la protección contra la úlcera gástrica y el estrés oxidativo

Lentinus squarrosulus (Mont.) mycelium enhanced antioxidant status in rat model

Nor Adila Mhd Omar,1,2 Sumaiyah Abdullah,1,3 Noorlidah Abdullah,1 Umah Rani Kuppusamy,1,4 Mahmood Ameen Abdulla,1,4 Vikineswary Sabaratnam11Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 2Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Gambang, Kuantan, Pahang, Malaysia; 3Department of Plant Protection, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 4Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaAim: Lentinus squarrosulus is an edible wild mushroom commonly found in Asia. This species has several interesting features such as rapid mycelial growth, and hence has the potential to be used as food, functional food, and nutraceuticals. Our previous study shows that L. squarrosulus contains potent antioxidant compounds in vitro. This study aims to investigate the in vivo bioavailability of L. squarrosulus mycelium extract and its antioxidant effect on biomarkers of antioxidant defense and oxidative stress.Methods: Water extract of mycelial biomass of L. squarrosulus was analyzed for in vivo antioxidant effects, including cupric-reducing antioxidant capacity (CUPRAC), glutathione peroxidase (GPx), xanthine oxidase (XO), advanced oxidation protein products (AOPPs), and lipid hydroperoxides (LHPs) at 0 and 28 days. GPx and XO were also analyzed in liver homogenates. Normal Sprague Dawley rats were treated with 250 and 500 mg/kg of extract for 28 days.Results: The serum CUPRAC level increased after treatment with both concentrations, indicating that there was sufficient bioavailability of the extract which contributed to the total antioxidant capacity. GPx activity in both serum and liver was increased and this correlated with LHP level after treatment with 250 mg/kg of extract, but XO activity was significantly decreased after treatment with 500 mg/kg of the extract. Lack of difference between AOPP levels implied that there were no significant changes in oxidative damage of protein after treatment.Conclusion: This study clearly showed that L. squarrosulus mycelium antioxidant extract contains absorbable antioxidants that enter the circulating plasma and cause a significant acute increase in plasma antioxidant capacity. Thus, the water extract of L. squarrosulus mycelium, which can be obtained abundantly by liquid fermentation, may serve as an antioxidant ingredient in functional foods and nutraceuticals.Keywords: mushroom, mycelia, CUPRAC, GPx, AOPP, xanthine oxidas