RESUMEN
Diabetic nephropathy (DN) is one of the most important complications of diabetesï¼ and the leading cause of end-stage renal disease (ESRD). While Chromium picolinate (CrPic) supplementation has been found to be effective in treating diabetes, its effects on diabetic-induced nephropathy have not been studied. Therefore, in this study, CrPic (1 mg kg -1 d -1) was administered to a DN rat model by oral gavage for eight weeks to investigate its effects. The results show that CrPic supplementation caused a decrease in levels of blood glucose, serum insulin, blood urea nitrogen (BUN), serum creatinine, and urinary albumin in DN rats. It also reversed renal pathological changes, including renal glomerular sclerosis and interstitial fibrosis. In addition, the oxidative defense system in the kidneys of DN rats was found to be improved; the biological activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) increased; and the content of malondialdehyde (MDA) lowered. Immunohistochemical results reveal that the expression levels of renal transforming growth factor-ß1 (TGF-ß1), Smad 2, and Smad 3 decreased significantly in the kidneys of rats in the CrPic-treated group. CrPic administration was thus found to ameliorate diabetic nephropathy in SD rats via an antioxidative stress mechanism, as well the ability to inhibit TGF-ß1/Smad2/3 expression. This study suggests that CrPic could be a potential renal-protective nutrient against diabetic nephropathy.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Ácidos Picolínicos/farmacología , Animales , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Fibrosis , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To explore the protective effect and mechanism of total flavones of Bidens pilosa L. (TFB) on IgA1 induced injury of venous endothelial cells in Henoch-Schönlein purpura (HSP) children patients. METHODS Human umbilical venous endothelial cells (HUVECs) were taken as subject. They were intervened by normal IgA1 and HSP children patients' serum IgA1, and added with different concentrations TFB at the same time. Then they were divided into the blank control group, the normal control group, the HSP IgA1 group, and HSP IgA1 plus TFB (1.0, 0.5, 0.25 mg/mL) groups. Levels of TNF-α and IL-8 in supernate were detected by ELISA. The NO level was detected by nitrate reductase method. mRNA and protein expressions of NF-κB and ICAM-1 in HUVECs were detected by fluorescent quantitative PCR and Western blot respectively. RESULTS: Compared with the normal control group and the blank control group, levels of IL-8, TNF-α, and NO all significantly increased in the HSP group (P < 0.05). Compared with the HSP group, levels of IL-8, TNF-α, and NO significantly decreased after intervention of TFB (1.0 and 0.5 mg/mL; P < 0.05, P < 0.01). Results of fluorescent quantitative PCR and Western blot showed, as compared with the blank control group and the normal control group, mRNA and protein expressions of NF-κB and ICAM-1 in HSP children patients' serum IgA1 induced venous endothelial cells significantly increased with statistical difference (P < 0.05, P < 0.01). Compared with the HSP group, mRNA and protein expressions of NF-KB and ICAM-1 were obviously down-regulated after intervention of TFB (1.0, 0.5, 0.25 mg/mL), with statistical difference (P < 0.05, P < 0.01). CONCLUSION: TFB could protect vascular damage by inhibiting in vivo high expression of NF-κB, reducing the production of IL-8, TNF-α, and NO in vascular endothelial cells of HSP children patients.
Asunto(s)
Bidens/química , Flavonas/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Vasculitis por IgA/sangre , Inmunoglobulina A/sangre , Niño , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-8/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: Bidens bipinnata L. is well known as a traditional antipyretic, anti-inflammatory and anti-rheumatic medicine in China. This study was designed to evaluate the role of total extracted flavonoids from B. bipinnata (TFB) in inhibiting the production of inflammatory cytokines. METHODS: Human umbilical vein endothelial cells (HUVEC) were used to examine the effect of TFB on the production of inflammatory cytokines. The supernatant interleukin (IL)-8, tumour necrosis factor (TNF)-α and nitric oxide (NO) levels of HUVEC were measured with ELISA methods. Nuclear factor-kappaB (NF-κB) and fractalkine expression was evaluated by RT-PCR and Western blot methods, respectively. KEY FINDINGS: We observed that IL-8, TNF-α and NO release of HUVEC incubated with sera from active Henoch-Schönlein purpura (HSP) was significantly increased. TFB intervention may significantly suppressed the supernatant IL-8, TNF-α and NO levels of HUVEC. Similarly, TFB obviously suppressed the NF-κB and fractalkine mRNA and protein expression. CONCLUSIONS: These results suggested that TFB may be useful for improving microvascular inflammation in HSP patients.
Asunto(s)
Antiinflamatorios/uso terapéutico , Bidens/química , Citocinas/biosíntesis , Flavonoides/uso terapéutico , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Vasculitis por IgA/tratamiento farmacológico , Fitoterapia , Antiinflamatorios/farmacología , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Niño , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Vasculitis por IgA/genética , Vasculitis por IgA/inmunología , Vasculitis por IgA/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-8/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , ARN Mensajero/metabolismo , Suero/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.
Asunto(s)
Bidens/química , Flavonoides/uso terapéutico , Cirrosis Hepática/prevención & control , Hígado/efectos de los fármacos , Actinas/genética , Actinas/metabolismo , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Tetracloruro de Carbono , Colágeno Tipo III/metabolismo , Relación Dosis-Respuesta a Droga , Flavonoides/química , Flavonoides/farmacología , Glutatión Peroxidasa/metabolismo , Hidroxiprolina/metabolismo , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Fitoterapia , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Bazo/efectos de los fármacos , Bazo/metabolismo , Bazo/patología , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Quinasa de Factor Nuclear kappa BRESUMEN
The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation.
Asunto(s)
Bidens/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Cirrosis Hepática/patología , Cirrosis Hepática/prevención & control , Enfermedad Aguda , Animales , Tetracloruro de Carbono/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Masculino , Malondialdehído/sangre , Ratones , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismoRESUMEN
Bidens bipinnata L. is well known in China as a traditional Chinese medicine. This study was designed to evaluate the hepatoprotective activity of the total flavonoids of B. bipinnata L. (TFB) against carbon tetrachloride (CCl4)-induced acute liver injury in mice and to determine its mechanism of action. Oral administration of TFB at doses of 50, 100 and 200 mg kg(-1) for 7 days significantly reduced the elevated relative values of liver weight, serum transaminases (alanine aminotransferase and aspartate aminotransferase) and the hepatic morphologic changes induced by CCl4 in mice. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, pretreatment with TFB suppressed nitric oxide production and nuclear factor-kappaB activation in CCl4-treated mice. The results suggest that TFB has significant hepatoprotective activity and its mechanism is related, at least in part, to its antioxidant properties. Further research is required to investigate the detailed mechanism of the protective effect of TFB on acute liver injury.
Asunto(s)
Bidens/química , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Flavonoides/uso terapéutico , Hígado/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Enfermedad Aguda , Animales , Antioxidantes/metabolismo , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Intoxicación por Tetracloruro de Carbono/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Depuradores de Radicales Libres/uso terapéutico , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , FN-kappa B/biosíntesis , Óxido Nítrico/biosíntesis , Tamaño de los Órganos , Fitoterapia , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To screen macroporous resins for isolation and purification of total flavonoids of Bidens bipinnata L. (TFB) through investigating the property of adsorption and desorption of 7 kinds of macroporous adsorption resins for TFB. METHODS: The content of total flavonoids was used as the evaluating criteria, and the static and dynamic adsorption-desorption methods were adopted to compare the adsorption quantity, the rate of desorption and adsorption kinetics of different macroporous adsorption resins. RESULTS: Among 7 kinds of macroporous adsorption resins, the HPD 100 resin was the best for isolating and purifying TFB. CONCLUSION: HPD 100 possess a better adsorbability and separating property, and its property is obviously higher than any other resins.
Asunto(s)
Bidens/química , Flavonoides/aislamiento & purificación , Adsorción , Medicamentos Herbarios Chinos , Cinética , PorosidadRESUMEN
This study was to investigate the effect of total flavones of rhododendra (TFR) on ischemic myocardial injury in rabbits. Rabbit ischemic myocardial injury was induced by occluding the anterior descent of the left artery (LAD). The ECG was recorded; the plasma creatine kinase (CK), nitric oxide (NO) and endothelin-1 (ET-1) levels were measured using spectrophotometry, Griess method and radioimmunoassay, respectively. The myocardial ischemic size and infarction size were determined by dual staining with Evan's blue and Nitroblue tetrazolium reductionest (N-BT). A typical ECG S-T segment elevation and an increase of plasma CK activity were observed 6 and 24 hours after the induction of ischemia. These changes were inhibited in rabbits treated with either TFR (30, 60 mg/kg) or ginkgo biloba extract (EGB) for 7 days, indicating a protective effect of TFR on ischemic myocardial injury. The myocardial ischemic size and infarction size were 40.7 +/- 3.6% and 36.8 +/- 3.6% respectively in the control group, while TFR (60 mg/kg) pretreatment for 7 days significantly reduced both myocardial ischemic size (32.40 +/- 5.38%, p < 0.05) and infarction size (28.7 +/- 5.8%, p < 0.05). In addition, the occlusion of LAD resulted in an increase of ET-1 and a decrease of NO levels in the plasma, effects that were inhibited by TFR treatment, suggesting a possible mechanism for the protective effect of TFR against myocardial ischemic injury.