RESUMEN
BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.
Asunto(s)
Infarto del Miocardio/patología , Extractos Vegetales/farmacología , Rheum , Animales , Creatina Quinasa/sangre , Relación Dosis-Respuesta a Droga , Isoproterenol/farmacología , L-Lactato Deshidrogenasa/sangre , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Distribución Aleatoria , Ratas , Ratas Wistar , Superóxido Dismutasa/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Chestnut flowers were one of the by-products during chestnut industrial processing. Chestnut (Castanea mollissima Blume) flower is rich in flavonoids and has been used as a traditional medicine to treat a variety of diseases including respiratory disorders for a long history. AIM OF THE STUDY: The present study aims to investigate the potential anti-inflammatory effect of flavonoids from chestnut flower (FCF) in lipopolysaccharide (LPS)-treated RAW 264.7 cells and stimulated acute lung injury (ALI) in mice. MATERIALS AND METHODS: HPLC-ESI-MS/MS was applied to identify flavonoids from Chestnut flower. The ROS content in cells and lung tissue was measured by flow cytometry. The malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and glutathione (GSH) content in cells and bronchoalveolar lavage fluid (BALF) was analyzed by photometry. Furthermore, the level of pro-inflammatory factors was analyzed by ELISA, and the expression of inflammatory gene mRNA by fluorescence quantitative PCR. H&E staining was used to evaluate the degree of lung tissue injury in mice. MPO activity was used to measure the degree of neutrophil infiltration. Total protein content was detected by BCA method. RESULTS: A total of forty-nine flavonoids compounds were tentatively identified in FCF by mass spectrometry analysis. The results of cell experiment suggested that FCF could alleviate oxidative injury via increasing SOD activity and GSH content, as well as inhibiting the production of intracellular ROS and MDA. FCF exerted its protective effect by suppressing the expression of both inducible nitric oxide synthase (iNOS) and cycooxygenase 2 (COX-2) to inhibit the synthesis of pro-inflammatory factors and cytokines, including NO, PGE2, TNF-α, IL-6 and IL-1ß. Besides, FCF treatment could alleviate the thickening of alveolar wall and pulmonary congestion in LPS-treated ALI mice, and significantly inhibit the activity of myeloperoxidas (MPO) and the expression of cytokines in BALF. CONCLUSIONS: FCF could ameliorate inflammation and oxidative stress in LPS-treated inflammation, resulting in an overall improvement in both macroscopic and histological parameters.
Asunto(s)
Lesión Pulmonar Aguda/patología , Antiinflamatorios/farmacología , Flavonoides/farmacología , Extractos Vegetales/farmacología , Animales , Líquido del Lavado Bronquioalveolar/citología , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Citocinas/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Flores , Glutatión/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Macrófagos/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Distribución Aleatoria , Superóxido Dismutasa/efectos de los fármacos , Espectrometría de Masas en TándemRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Several Amomum species are commonly used in food as flavoring agents and traditional Chinese medicine to treat inflammation-related diseases. AIM OF THE STUDY: This study aims to investigate the protective effects of Chinese herbal medicines, including six Amomum Roxb. essential oils (AEOs), against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. MATERIALS AND METHODS: The compositions of AEOs were analyzed using gas chromatography - mass spectrometry. RAW264.7 cells were treated with AEOS (0-100 µg/mL) and stimulated with LPS. C57 mice received AEOs (100 mg/kg) via atomization system for seven consecutive days, and then, intratracheal instillation of LPS was applied to establish an in vivo model of acute lung injury. RESULTS: We identified three AEOs demonstrating anti-inflammatory effects and amelioration of LPS-induced lung tissue pathological damage. Furthermore, we found that these AEOs reduced lung wet/dry weight ratios and protein concentrations in the bronchoalveolar lavage fluid of mice with LPS-induced ALI. Additionally, AEOs reduced the levels of malondialdehyde, TNF-α, IL-6, and IL-1ß but increased the levels of superoxide dismutase and catalase in lung tissue, alveolar lavage fluid, and serum samples. We also found that these three AEOs affected proteins related to the TLR4/Myd88/NF-κB pathway. CONCLUSIONS: In summary, our findings revealed that AEOs ameliorate inflammatory and oxidative stress in mice with ALI through the TLR4/Myd88/NF-κB pathway.
Asunto(s)
Lesión Pulmonar Aguda/patología , Amomum , Aceites Volátiles/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar/química , Catalasa/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Masculino , Glicoproteínas de Membrana/efectos de los fármacos , Metabolómica , Ratones , Ratones Endogámicos C57BL , FN-kappa B/efectos de los fármacos , Células RAW 264.7 , Distribución Aleatoria , Superóxido Dismutasa/efectos de los fármacos , Receptor Toll-Like 4/efectos de los fármacosRESUMEN
ß-Boswellic acid (ß-BA) and 11-keto-ß-boswellic acid (ß-KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of ß-BA and ß-KBA with detailed parameters. This research revealed that treatment with ß-BA and ß-KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the ß-BA and ß-KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of ß-BA and ß-KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of ß-BA and ß-KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of ß-BA and ß-KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects of ß-BA and ß-KBA suggest these compounds as potential therapeutics for diabetic conditions.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Extractos Vegetales/farmacología , Triterpenos/farmacología , Animales , Glucemia/efectos de los fármacos , Boswellia , Dipeptidil Peptidasa 4/farmacología , Relación Dosis-Respuesta a Droga , Lípidos/sangre , Malondialdehído/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Estreptozocina , Superóxido Dismutasa/efectos de los fármacos , Triterpenos/administración & dosificación , Pérdida de Peso/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is commonly used in traditional medicine as a tonic for rejuvenation and exhibiting good antioxidant activities. AIM OF THE STUDY: To evaluate P. longifolia methanolic leaf extract (PLME) antiaging activity at 1 mg/mL in Saccharomyces cerevisiae BY611 yeast. MATERIALS AND METHODS: The antiaging effect of PLME was studied via replicative lifespan assay, antioxidative stress assays, reactive oxygen species (ROS) determination, reduced glutathione (GSH) determination, superoxide dismutase (SOD) and Sirtuin 1 (SIRT1) genes regulation studies and SOD and SIRT1 proteins activities. RESULTS: The PLME treatment increased the growth and prolonged the lifespan of the yeast significantly (p < 0.05) compared to the untreated yeast group. Besides, the PLME also protected the yeast from oxidative stress induced by 4-mM-H2O2 via decreasing (p < 0.05) the ROS from 143.207 to 127.223. The antioxidative action of PLME was proved by spot assay. Phloxine B staining was further confirmed the PLME antioxidative action of PLME, where more whitish-pink live yeast cells were observed. In addition, the PLME also enhanced GSH content significantly (p < 0.05) in yeast treated with PLME from 16.81 to 25.31 µmol. Furthermore, PLME increased the SOD and SIRT1 genes expression significantly (p < 0.05) with ΔCt values of 1.11 and 1.15, respectively. The significantly (p < 0.05) elevated SOD and SIRT1 protein activities were recorded as 51.54 U/mg Prot and 1716 ng/mL, respectively. CONCLUSIONS: PLME exhibited good antiaging activities in S. cerevisiae, by modulating oxidative stress, enhancing GSH content, and increasing SOD and SIRT1 genes expression.
Asunto(s)
Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Polyalthia/química , Polifenoles/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sirtuina 1/efectos de los fármacos , Superóxido Dismutasa/efectos de los fármacosRESUMEN
SUMMARY: Carnosine is known as a natural dipeptide, which inhibits the proliferation of tumor cells throughout its action on mitochondrial respiration and cell glycolysis. However, not much is known about its effects on the metabolism of healthy cells. We explored the effects of Karnozin EXTRA® capsule with different concentrations of L-carnosine, on the cell viability and the expressions of intermediate filament vimentin (VIM) and superoxide dismutase (SOD2) in normal fibroblasts BHK-21/C13. Furthermore, we investigated its action on the energy production of these cells. Cell viability was quantified by the MTT assay. The Clark oxygen electrode (Oxygraph, Hansatech Instruments, England) was used to measure the "intact cell respiration rate", state 3 of ADP-stimulated oxidation, maximum oxidation capacity and the activities of complexes I, II and IV. Results showed that Karnozin EXTRA® capsule in concentrations of 2 and 5 mM of L-carnosine did not induce toxic effects and morphological changes in treated cells. Our data revealed a dose-dependent immunofluorescent signal amplification of VIM and SOD2 in the BHK-21/C13 cell line. This supplement substantially increased the recorded mitochondrial respiration rates in the examined cell line. Due to the stimulation of mitochondrial energy production in normal fibroblasts, our results suggested that Karnozin EXTRA® is a potentially protective dietary supplement in the prevention of diseases with altered mitochondrial function.
RESUMEN: La carnosina se conoce como dipéptido natural, que inhibe la proliferación de células tumorales a través de su acción sobre la respiración mitocondrial y la glucólisis celular. Sin embargo, no se sabe mucho de sus efectos sobre el metabolismo de las células sanas. Exploramos los efectos de la cápsula Karnozin EXTRA® con diferentes concentraciones de L-carnosina, sobre la viabilidad celular y las expresiones de vimentina de filamento intermedio (VIM) y superóxido dismutasa (SOD2) en fibroblastos normales BHK-21 / C13. Además, estudiamos su acción sobre la producción de energía de estas células. La viabilidad celular se cuantificó mediante el ensayo MTT. Se utilizó el electrodo de oxígeno Clark (Oxygraph, Hansatech Instruments, Inglaterra) para medir la "tasa de respiración de células intactas", el estado 3 de oxidación estimulada por ADP, la capacidad máxima de oxidación y las actividades de los complejos I, II y IV. Los resultados mostraron que la cápsula de Karnozin EXTRA® en concentraciones de 2 y 5 mM de L- carnosina no indujo efectos tóxicos ni cambios morfológicos en las células tratadas. Nuestros datos revelaron una amplificación de señal inmunofluorescente dependiente de la dosis de VIM y SOD2 en la línea celular BHK-21 / C13. Este suplemento aumentó sustancialmente las tasas de respiración mitocondrial registradas en la línea celular examinada. Debido a la estimulación de la producción de energía mitocondrial en fibroblastos normales, nuestros resultados sugirieron que Karnozin EXTRA® es un suplemento dietético potencialmente protector en la prevención de enfermedades con función mitocondrial alterada.
Asunto(s)
Animales , Carnosina/farmacología , Fibroblastos/efectos de los fármacos , Riñón/citología , Superóxido Dismutasa/efectos de los fármacos , Vimentina/efectos de los fármacos , Bioensayo , Supervivencia Celular/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Cricetinae , Técnicas de Cultivo de Célula , Metabolismo EnergéticoRESUMEN
Benzene can impair peripheral immunity and immune organs; however, the recovery of benzene impairment has rarely been reported. In this study, we developed an immune dysfunction mouse model using a benzene gavage (500 mg/kg). Female Balb/c mice were treated with Bombyx batryticatus (BB, 5 g/kg), raw pinellia (RP, 5 g/kg), or a combination of Valproic acid and Coenzyme Q10 (CM, 150 mg/kg VPA & 100 mg/kg CoQ10) medication for four weeks. The immune function of the peripheral blood mononuclear cells (PBMCs), spleen, and thymus was determined to evaluate whether the observed impairment could be altered by medications in the mouse model. Results showed that medications could alleviate benzene-induced structural and functional damage of spleen and thymus. Benzene exposure decreased the ATP level of PBMC, which can be improved by BB, RP or CM. Importantly, BB, RP or CM could relieve benzene induced-oxidative stress by increasing the activities of glutathione peroxidase (GSH) and superoxide dismutase (SOD) and decreasing the contents of malondialdehyde (MDA). In conclusion, BB, RP, and CM were able to alleviate the benzene-induced immune dysfunction and redox imbalance. Improvement of the oxidative and antioxidant imbalance may represent a mechanism by which medicine prevents benzene-induced immune dysfunction.
Asunto(s)
Benceno/toxicidad , Inmunidad/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Bazo/efectos de los fármacos , Timo/efectos de los fármacos , Adenosina Trifosfato/sangre , Animales , Bombyx/química , Femenino , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Pinellia/química , Extractos Vegetales/farmacología , Organismos Libres de Patógenos Específicos , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Ubiquinona/farmacología , Ácido Valproico/farmacologíaRESUMEN
Pulmonary hypertension (PH) is a global health issue with a prevalence of 10% in ages >65 years. Right heart failure (RHF) is the main cause of death in PH. We have previously shown that monocrotaline (MCT)-induced PH and RHF are due to an increase in oxidative stress. In this study, probucol (PROB), a strong antioxidant with a lipid-lowering property, versus lovastatin (LOV), a strong lipid-lowering drug with some antioxidant effects, were evaluated for their effects on the MCT-induced RHF. Rats were treated (I.P.) with PROB (10 mg/kg ×12) or LOV (4 mg/kg ×12), daily 6 days before and 6 days after a single MCT injection (60 mg/kg). Serial echocardiography was performed and at 4-week post-MCT, lung wet-to-dry weight, hemodynamics, RV glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase, lipid peroxidation, and myocardial as well as plasma lipids were examined. MCT increased RV systolic and diastolic pressures, wall thickness, RV end diastolic diameter, mortality, and decreased ejection fraction as well as pulmonary artery acceleration time. These changes were mitigated by PROB while LOV had no effect. Furthermore, PROB prevented lipid peroxidation, lowered lipids, and increased GSHPx and SOD in RV myocardium. LOV did decrease the lipids but had no effect on antioxidants and lipid peroxidation. A reduction in oxidative stress and not the lipid-lowering effect of PROB may explain the prevention of MCT-induced PH, RHF, and mortality. Thus targeting of oxidative stress as an adjuvant therapy is suggested.
Asunto(s)
Anticolesterolemiantes/farmacología , Antioxidantes/farmacología , Insuficiencia Cardíaca/metabolismo , Corazón/efectos de los fármacos , Hipertensión Pulmonar/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Lovastatina/farmacología , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Probucol/farmacología , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Ecocardiografía , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Pulmón/efectos de los fármacos , Monocrotalina/toxicidad , Tamaño de los Órganos/efectos de los fármacos , Ratas , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Disfunción Ventricular Derecha/inducido químicamente , Disfunción Ventricular Derecha/tratamiento farmacológico , Disfunción Ventricular Derecha/metabolismo , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
This work aims to analyze the effect of the ethanol extract from Polygonatum odoratum on high glucose-induced tubular epithelial cell apoptosis and oxidative stress. HK-2 injury of tubular epithelial cells was induced by high glucose, and the ethanol extract from Polygonatum odoratum was given. HK-2 cell activity and apoptosis were detected by MTT method and flow cytometry, respectively. Western blot was performed to analyze Cleaved-caspase3, Pro-caspase3, Nrf2, HO-1 protein expression. The levels of MDA, GSH, SOD were evaluated using commercial Kit. si-Nrf2 was transfected into HK-2 cells and high-glucose induction and ethanol extract from Polygonatum odoratum were given to observe the changes of cell apoptosis and oxidative stress. Ethanol extract from Polygonatum odoratum increased the high glucose-induced HK-2 cell activity, Pro-caspase3, Nrf2, HO-1 protein, GSH, SOD levels and decreased its apoptosis rate, Cleaved-caspase3 protein and MDA levels, showing statistically significant difference (p<0.05). After Nrf2 interference, high glucose-induced HK-2 cell activity, Pro-caspase3 protein, GSH, and SOD levels were decreased under the action of ethanol extract from Polygonatum odoratum, while the apoptosis rate, Cleaved-caspase3 protein, and MDA levels were increased significantly (p<0.05). The ethanol extract from Polygonatum odoratum can inhibit high glucose-induced tubular epithelial cell apoptosis and reduce oxidative stress by activating the Nrf2-ARE signaling pathway.
Asunto(s)
Apoptosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Glucosa/farmacología , Túbulos Renales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Polygonatum , Western Blotting , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular , Nefropatías Diabéticas , Etanol , Citometría de Flujo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Hemo-Oxigenasa 1/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Humanos , Túbulos Renales/citología , Malondialdehído/metabolismo , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
This experiment proposed to study the efficiency omega 3 fatty acid on behavioural phenotype of Parkinson's disease (PD) in mice. Totally 7 groups (each group 6 mice) were used in this assessment, each groups were treated with saline (control), MPP+, L-DOPA, Omega 3 oil, Omega 3 oil (three different concentrations) +MPP+ separately. The behavioral assessments such as bar test, open field test, maze test, hang test were noted on 7th, 14th, 21st and 28th day. After the examination period, the tested animals' midbrains and frontal cortex were dissected to analyze TBARS, GSH, Catalase, Superoxide Dismutase and Glutathione Peroxidase assay. In the bar test, 500mg omega 3 fatty acid administrated mice showed a high cataleptic scores. In open field Test, significant reductions in behavior analysis were observed from the tested mice group. Maze test and hang test doesn't show much difference. In biochemical test, tested groups showed promising results compared to control group. The result strongly proved that the omega 3 fatty acid has remarkable abilities to control the neurodegenerative diseases.
Asunto(s)
Antiparkinsonianos/farmacología , Conducta Animal/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Estrés Oxidativo/efectos de los fármacos , Trastornos Parkinsonianos/fisiopatología , 1-Metil-4-fenilpiridinio/toxicidad , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Reacción Cataléptica de Congelación , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Levodopa/farmacología , Masculino , Mesencéfalo/efectos de los fármacos , Mesencéfalo/metabolismo , Ratones , Prueba de Campo Abierto , Trastornos Parkinsonianos/inducido químicamente , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Salicylic acid, a phenolic compound, found in plants, possesses free radical scavenging and iron chelation properties. The present study is designed to study the antioxidant effect of salicylic acid in gentamicin induced nephrotoxicity in rabbits. For this purpose twenty four male albino rabbits were divided into 4 groups (n=6); control group, healthy untreated rabbits, gentamicin group, received only gentamicin (80mg/kg), gentamicin + salicylic acid group, received gentamicin (80mg/kg) + salicylic acid (80mg/kg) and salicylic acid group, received only salicylic acid (80mg/kg) via intra peritoneal route for 21 consecutive days. Biochemical evaluation was carried out by assessment of body weights and by estimating renal function tests (plasma urea, plasma creatinine and plasma uric acid), tissue antioxidant enzymes (catalase, SOD) and MDA level. Gentamicin induction resulted in decreased body weights, increased plasma urea, plasma creatinine, plasma uric acid, tissue MDA level and decreased tissue SOD and tissue catalase activity in gentamicin treated group which was restored by supplementation with salicylic acid in gentamicin + salicylic acid group. Our data suggests that supplementation of salicylic acid can be useful in reducing gentamicin induced nephrotoxicity in rabbits.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antibacterianos/toxicidad , Antioxidantes/farmacología , Gentamicinas/toxicidad , Riñón/efectos de los fármacos , Ácido Salicílico/farmacología , Lesión Renal Aguda/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Creatinina/sangre , Riñón/metabolismo , Malondialdehído/metabolismo , Conejos , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Urea/sangre , Ácido Úrico/sangreRESUMEN
The intention to conduct this study was to evaluate the hepatoprotective effects of Fenugreek seeds' extract supplementation in thioacetamide induced liver damage in male Sprague Dawley rats. For this study, 24 male Sprague Dawley rats (200-264gm) were distributed randomly into four groups. Group I remained untreated as control rats, group II received thioacetamide (200mg/Kg b.w i.p, administered on alternative days for 8 weeks), group III received thioacetamide (200mg/Kg b.w i.p administered on alternative days for 8 weeks) as well as 2ml of 2% extract of fenugreek seeds (orally administered daily from 4th week till 8th week of the experiment. Group IV only received 2ml of 2% extract of Fenugreek seeds daily for 4 weeks respectively. At the end of the experiment, blood was sampled to obtain plasma that was used for the analysis of liver markers and liver was used for analysis of antioxidant enzymes (catalase and SOD). Increase in total bilirubin, direct bilirubin, ALT and ALP levels, catalase activity and decrease in SOD activity was found in TAA-treated groups which assured liver damage. Whereas, treatment with Fenugreek seeds extract restored the altered levels of total bilirubin, direct bilirubin, ALT, ALP, catalase and SOD activities in the Test + Supp group. The results of this study confirmed the hepatoprotective role of Fenugreek seeds extract in thioacetamide induced liver damage.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Tioacetamida/toxicidad , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Antioxidantes/metabolismo , Bilirrubina/metabolismo , Peso Corporal/efectos de los fármacos , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado/metabolismo , Hígado/patología , Tamaño de los Órganos/efectos de los fármacos , Distribución Aleatoria , Ratas , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , TrigonellaRESUMEN
To evaluate in-vivo antioxidant potential of fruit mucilage from Cucumis melo variety momordica (PM) and variety agrestis (KM) using rats as experimental animals, the fruits were collected, identified, dried and pulverized. Mucilages were isolated from the fruit powders by microwave-assisted method. Aqueous extracts obtained were filtered to remove fruit pulp. Each filtrate was centrifuged at 4000xg rpm for 15 min. Each supernatant was precipitated with 3 volumes of 95% ethanol and maintained overnight at 4°C. These precipitates were filtered and lyophilized. In vivo antioxidant activity was determined using rats for 14 days. Paracetamol (75mg/Kg, i.p.) for inducing oxidative stress and Vitamin C & Vitamin E (200mg/Kg each, p.o.) as standard treatment were used. PM and KM were given in 500mg/Kg and 1000mg/Kg, p.o. doses in separate groups. SOD, MDA, GSH and CAT levels were estimated in organs (liver, kidney, heart, brain) of all groups using standard procedures. Toxic control showed prominent toxicity in the liver. The levels of GSH, CAT and SOD were raised and MDA levels were reduced in all organs of test and standard groups. The levels of antioxidant biomarkers varied in all remaining groups. The overall results are significant suggesting strong antioxidant potential of PM and KM.
Asunto(s)
Antioxidantes/farmacología , Cucumis melo , Frutas , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/metabolismo , Ratas , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 µg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P = 0.03). The serum zinc level was significantly correlated with the MDA level (P = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 µmm2, P = 0.04). Conclusions: The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.
Asunto(s)
Degeneración Macular/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Acetato de Zinc/uso terapéutico , Anciano , Biomarcadores , Cobre/administración & dosificación , Cobre/sangre , Quimioterapia Combinada , Femenino , Glutatión Peroxidasa/efectos de los fármacos , Humanos , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , Drusas del Disco Óptico/patología , Estudios Prospectivos , Superóxido Dismutasa/efectos de los fármacos , Agudeza Visual , Zinc/administración & dosificación , Zinc/sangreRESUMEN
Present investigation was carried out to evaluate the antioxidant and haematinic effects of methanolic (MREt) and aqueous methanolic (AqMREt) root extracts of R. serpentina in mice model of type 2 diabetes (T2D). Experimental mice were divided into nine groups (six per group) as: fructose-induced (T2D) diabetic group (distilled water 1ml/kg), negative control (0.05% DMSO 1ml/kg), positive control (pioglitazone 15mg/kg) and six test groups (MREt 10, 30 & 60mg/kg & AqMREt 50, 100 & 150mg/kg). Whereas tenth group was served as normal control (1ml/kg distilled water). All test doses of MREt & AqMREt significantly (p<0.05) decreases the percent inhibition of catalase (CAT) and superoxide dismutase (SOD) when compared with diabetic controls. Treatment with both extracts also improved the total hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC) counts, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) in test groups. Fourier transform infrared (FTIR) spectral analysis revealed the presence of phenols moiety in both extracts. Findings suggested that AqMREt possesses more antioxidant and haematinic potential while the MREt of R. serpentina moderately possesses the same activities, which might be due to the high content of phenols present in AqMREt.
Asunto(s)
Antioxidantes/farmacología , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 2/sangre , Índices de Eritrocitos/efectos de los fármacos , Hematínicos/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas , Rauwolfia , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Recuento de Eritrocitos , Hematócrito , Hemoglobinas/efectos de los fármacos , Hemoglobinas/metabolismo , Recuento de Leucocitos , Ratones , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Studied the optimum extraction process of polysaccharide from Phaeoporus obliquus and the effect of Phaeoporus obliquus polysaccharide on carbon tetrachloride (CCl4)- or alcohol-induced acute liver injury in mice. The main factor in influencing the extraction rate of Phaeoporus obliquus polysaccharide were extraction power and time, which was a kind of pyran glucose by infrared spectroscopy. CCl4 and alcohol were employed respectively to establish CCl4 and alcohol-induced acute liver injury mouse models. Compared with model groups mice, Phaeoporus obliquus polysaccharide treatment at the doses of 100mg/kg and 200mg/kg exhibited an obvious reduction liver index, ALP, ALT, AST levels, MDA content and TNF-α level (p<0.01) and SOD activity was increased, which was in a dose-dependent manner. Compared with the model group, the necrosis degree of hepatocytes was obviously reduced and the small fat droplets were formed in some cytoplasm, especially in high dose group, which the liver cells recovered to the level of normal group. Rt-PCR results showed that the expression of CYP2E1 mRNA in liver tissues of Phaeoporus obliquus polysaccharide groups were significantly reduced, and the difference were statistically significant compared with the model group (p<0.05). These results demonstrated that Phaeoporus obliquus polysaccharide has significantly hepatoprotective effect on CCl4 and alcohol-induced acute liver injury in mice.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Polisacáridos Fúngicos/farmacología , Hepatocitos/efectos de los fármacos , Inonotus , Hepatopatías Alcohólicas/metabolismo , Hígado/efectos de los fármacos , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Aspartato Aminotransferasas/metabolismo , Tetracloruro de Carbono/toxicidad , Depresores del Sistema Nervioso Central/toxicidad , Citocromo P-450 CYP2E1/efectos de los fármacos , Citocromo P-450 CYP2E1/genética , Etanol/toxicidad , Hepatocitos/metabolismo , Hepatocitos/patología , Hígado/metabolismo , Hígado/patología , Malondialdehído/metabolismo , Ratones , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Natural Plants are broadly used in treating inflammatory disorders. The current study focused on evaluating the hepato-protective and anti-inflammatory potential of A. modesta in MnCL2 induced hepatotoxicity and liver inflammation. The MnCl2 induce 6.0mg/kg was given for 30 days (p.o) to induced hepatotoxicity and liver inflammation. The ethanolic extract of A. modesta were given orally at the dose of 100mg/kg/day. The in vivo inflammatory manganese induced hepatotoxic model is used for evaluating the acacia heap to-protective effect. Gas chromatography-mass spectrometry analyses were performed to find out compounds responsible for anti-inflammatory properties. Results showed that administration of ethanolic extract (100 mg/kg), altogether diminished inflammation of the liver, expanded liver capacity, oxidative stress and his to-pathological outcomes in the current study compared with disease rats. The beneficial outcomes of A. modesta extract were observed on liver inflammation.
Asunto(s)
Acacia , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Cloruros/toxicidad , Inflamación/metabolismo , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Interleucina-18/genética , Interleucina-4/genética , Hígado/metabolismo , Hígado/patología , Compuestos de Manganeso , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Drug synergy is the combine effect of drug efficacy. Synergistic combinations of active ingredients have proven to be highly effective and more useful in therapeutics. In contrast, the individual effect of drug is usually undesirable and mostly used for selecting drug-resistant mutations. Purpose of this study was to check synergistic effects of both plants (Barbadensis miller and Marsdenia condurango) against liver and cervical cancer. METHODOLOGY: Culturing of HeLa (cervical cancer cell line) and HepG2 (liver cancer cell line) cells, IC50 evaluation, viability assays (trypan blue, crystal violet), p53 ELISA and immunocytochemistry, MUSE analysis (count and viability), antioxidants (GSH, SOD, CAT), at the end RT-PCR was performed. RESULTS: IC50 evaluation was done of each plant individually and with combination for synergistic effects, IC50 with plants combination (synergism) was applied on further viability assays (trypan blue, crystal violet, MUSE analysis via count and viability kit) p53 ELISA and immunocytochemistry for evaluation of cellular apoptosis, antioxidants assays (GSH, SOD, CAT), and RT-PCR with proliferative and apoptotic markers along with internal control. CONCLUSION: According to current study it was observed that synergistic effect of these plants has more anticancer properties with minimum effective dose. It was also observed that extracts possess the ability to induce apoptosis, restrict proliferation and enhanced oxidative stress.
Asunto(s)
Aloe , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas , Marsdenia , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Neoplasias del Cuello Uterino , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Células HeLa , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Fitoterapia , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The aim of this work was to evaluate the gastroprotective activity of a Mexican propolis on indomethacin-induced gastric ulcers in a mouse model. The following contents of the ethanolic extract of propolis of Chihuahua (EEPCh) were determined: antioxidant activity (SA50), total phenolic content (TPC), total flavonoid content (TFC), and chemical composition by HPLC-DAD and HPLC-MS, as well as acute toxicity by OECD Guideline 423. Gastric lesions were induced by intragastric indomethacin treatment in male ICR mice. As the positive control, omeprazole was administered, and three doses of EEPCh were evaluated (50, 150 and 300 mg/kg). Gastric mucosal injury, histological changes and mucosal content were evaluated by means of H&E and PAS staining. For homogenized gastric tissues, the following were evaluated: TBARS, MPO, and PGE2 levels; SOD and GPx antioxidant enzymatic activity; and the concentrations of the proinflammatory cytokines, TNF-α, IL-1ß and IL-6. EEPCh had a significant SA50 of 41.55 µg/mL. The TPC of EEPCh was 860 mg GAE/g, and its TFC was 49.58 mg QE/g. Different phenolic compounds were identified in the extract and were not toxic. The EEPCh doses decreased mucosal damage and histological injuries, maintained the mucosal content and reduced the TBARS, MPO and concentrations of proinflammatory cytokines in gastric ulcer tissues. The 150 and 300 mg/kg doses increased the SOD activity and maintained the PGE2 content. Only the 300 mg/kg dose increased the GPx activity. The results of this study suggest that EEPCh displays gastroprotective effects by means of its antioxidant activity and anti-inflammatory effects and promotes ulcer protection through the maintenance of mucosal content and PGE2 levels.
Asunto(s)
Antiulcerosos/química , Antiulcerosos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Própolis/química , Própolis/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/uso terapéutico , Antioxidantes/análisis , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Femenino , Flavonoides/análisis , Flavonoides/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/lesiones , Mucosa Gástrica/patología , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Indometacina/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos ICR , Omeprazol/farmacología , Fenoles/análisis , Fenoles/química , Extractos Vegetales/uso terapéutico , Própolis/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
PURPOSE: Atherosclerosis, a chronic disease of the arteries, results from pathological processes including the accumulation and aggregation of oxidized low-density lipoprotein (oxLDL) in the vessel walls, development of neointima, formation of a fibrous cap, and migration of immune cells to damaged vascular endothelium. Recent studies have shown that mitochondrial dysfunction is closely associated with the development and progression of atherosclerosis. Idebenone, a short-chain benzoquinone similar in structure to coenzyme Q10, can effectively clear oxygen free radicals as an electron carrier and antioxidant. In the present study, we aim to investigate weather idebenone protects against atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. METHODS: apoE-/- mice receiving a high-fat diet (HFD) were treated with idebenone for 16 weeks. A total of 60 mice were randomized into the following four groups: (1) HFD, (2) HFD and low-dose idebenone (100 mg/kg/d), (3) HFD and medium-dose idebenone (200 mg/kg/d), and (4) HFD and high-dose (400 mg/kg/d). Proteomic analysis was performed between the HFD and idebenone-high-dose group. Plaque analysis was carried out by histological and immunohistochemical staining. Western blot, TUNEL staining, and MitoSOX assays were performed in human umbilical vein endothelial cells (HUVECs) to investigate the SIRT3-SOD2-mtROS pathway. RESULTS: Histological and morphological analysis demonstrated that idebenone significantly reduced plaque burden and plaque size. Idebenone treatment effectively stabilized the atherosclerotic plaques. In mice treated with idebenone, 351 up-regulated and 379 down-regulated proteins were found to be significantly altered in proteomic analysis. In particular, the expression of SIRT3, SOD2, and NLRP3 was significantly regulated in the idebenone treatment groups compared with the HFD group both in vivo and in vitro. We further confirmed that idebenone protected against endothelial cell damage and inhibited the production of mitochondrial reactive oxygen species (mtROS) in cholesterol-treated HUVECs. CONCLUSIONS: We demonstrated that idebenone acted as a mitochondrial protective agent by inhibiting the activation of NLPR3 via the SIRT3-SOD2-mtROS pathway. Idebenone may be a promising therapy for patients with atherosclerosis by improving mitochondrial dysfunction and inhibiting oxidative stress.