Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage. In this study, a focal cerebral ischemia/reperfusion injury model was e...Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage. In this study, a focal cerebral ischemia/reperfusion injury model was established using middle cerebral artery occlusion in mice. Both 62.5, 125, and 250 mg/kg oxysophoridine, via intraperitoneal injection, and 6 mg/kg nimodipine, via intragastric administration, were administered daily for 7 days before modeling. After 24 hours of reperfusion, mice were tested for neurological deficit, cerebral infarct size was assessed and brain tissue was collected. Results showed that oxysophoridine at 125, 250 mg/kg and 6 mg/kg nimodipine could reduce neurological deficit scores, cerebral infarct size and brain water content in mice. These results provided evidence that oxysophoridine plays a protective role in cerebral ischemia/reperfusion injury. In addition, oxysophoridine at 62.5, 125, and 250 mg/kg and 6 mg/kg nimodipine increased adenosine-triphosphate content, and decreased malondialdehyde and nitric oxide content. These compounds enhanced the activities of glutathione-peroxidase, superoxide dismutase, catalase, and lactate dehydrogenase, and decreased the activity of nitric oxide synthase. Protein and mRNA expression levels of N-methyl-D-aspartate receptor subunit NR1 were markedly inhibited in the presence of 250 mg/kg oxysophoridine and 6 mg/kg nimodipine. Our experimental findings indicated that oxysophoridine has a neuroprotective effect against cerebral ischemia/reperfusion injury in mice, and that the effect may be due to its ability to inhibit oxidative stress and expression of the N-methyl-D-aspartate receptor subunit NR1.展开更多
Objective:To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods:C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then d...Objective:To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods:C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then divided into 5 groups(14 per group),and treated with oxysophoridine(50,100,or 150 mg/kg) or cisplatin(4 mg/kg) for 10 days.Inhibitory rate of tumor,body weight gain,and influence indices on internal organs(liver,spleen and thymus) were evaluated.The differentially expressed genes between the oxysophoridine-treated group,and the control group were analyzed using cDNA microarray and quantitative real-time PCR(qRT-PCR) experiments.Results:Compared with the tumor weight of the control group(2.75±0.66 g),oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice(P<0.01),with 0.82±0.36 g,0.57±0.22 g,and 1.22±0.67 g for the tumor weight in the low,moderate,and high dose treatment group, respectively.The moderate dose led to the highest inhibitory rate,79.3%.Observation of body weight gain and influence on three organs showed that compared with cisplatin,oxysophoridine produced fewer side effects in vivo.cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis,with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected.Conclusion:Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma,and its anti-hepatoma effect was probably related to osteoprotegerin activation.展开更多
基金supported by the National Natural Science Foundation of China, No. 30960506, 81160524the Natural Science Foundation of Ningxia Hui Autonomous Region, No. NZ11212+1 种基金the Key Scientific Research Project of Ningxia Hui Autonomous Region Health Department, No. 2012152the Project of Ningxia Medical University, No. XM2011017
文摘Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage. In this study, a focal cerebral ischemia/reperfusion injury model was established using middle cerebral artery occlusion in mice. Both 62.5, 125, and 250 mg/kg oxysophoridine, via intraperitoneal injection, and 6 mg/kg nimodipine, via intragastric administration, were administered daily for 7 days before modeling. After 24 hours of reperfusion, mice were tested for neurological deficit, cerebral infarct size was assessed and brain tissue was collected. Results showed that oxysophoridine at 125, 250 mg/kg and 6 mg/kg nimodipine could reduce neurological deficit scores, cerebral infarct size and brain water content in mice. These results provided evidence that oxysophoridine plays a protective role in cerebral ischemia/reperfusion injury. In addition, oxysophoridine at 62.5, 125, and 250 mg/kg and 6 mg/kg nimodipine increased adenosine-triphosphate content, and decreased malondialdehyde and nitric oxide content. These compounds enhanced the activities of glutathione-peroxidase, superoxide dismutase, catalase, and lactate dehydrogenase, and decreased the activity of nitric oxide synthase. Protein and mRNA expression levels of N-methyl-D-aspartate receptor subunit NR1 were markedly inhibited in the presence of 250 mg/kg oxysophoridine and 6 mg/kg nimodipine. Our experimental findings indicated that oxysophoridine has a neuroprotective effect against cerebral ischemia/reperfusion injury in mice, and that the effect may be due to its ability to inhibit oxidative stress and expression of the N-methyl-D-aspartate receptor subunit NR1.
基金Supported by Tianjin Key Technology Research & Development Program(No.07ZCKFSH00200)
文摘Objective:To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods:C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then divided into 5 groups(14 per group),and treated with oxysophoridine(50,100,or 150 mg/kg) or cisplatin(4 mg/kg) for 10 days.Inhibitory rate of tumor,body weight gain,and influence indices on internal organs(liver,spleen and thymus) were evaluated.The differentially expressed genes between the oxysophoridine-treated group,and the control group were analyzed using cDNA microarray and quantitative real-time PCR(qRT-PCR) experiments.Results:Compared with the tumor weight of the control group(2.75±0.66 g),oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice(P<0.01),with 0.82±0.36 g,0.57±0.22 g,and 1.22±0.67 g for the tumor weight in the low,moderate,and high dose treatment group, respectively.The moderate dose led to the highest inhibitory rate,79.3%.Observation of body weight gain and influence on three organs showed that compared with cisplatin,oxysophoridine produced fewer side effects in vivo.cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis,with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected.Conclusion:Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma,and its anti-hepatoma effect was probably related to osteoprotegerin activation.
