Oxysophoridine

Planta Med. 2013 Jul;79(11):916-23.

Anti-apoptotic and neuroprotective effects of oxysophoridine on cerebral ischemia both in vivo and in vitro.[Pubmed: 23807812]

In this study, we investigated the neuroprotective effect of Oxysophoridine on ischemia and ischemia-like insults.
METHODS AND RESULTS:
Protection by Oxysophoridine was studied at the in vivo level using a model of middle cerebral artery occlusion in mice and at the in vitro level using primary rat hippocampal neuronal cultures exposed to oxygen-glucose deprivation, a model of ischemia-like injury. The quantitative real-time PCR assay was used to evaluate the release of cytochrome c and the expression of caspase-3 mRNA. Oxysophoridine-treated groups (62.5, 125, 250 mg/kg) markedly reduced neurological deficit scores and infarct volumes. Treatment with Oxysophoridine (5, 20, 80 µmol/L) significantly attenuated neuronal damage, with evidence of decreased cell apoptosis and decreased cell morphologic impairment. Furthermore, treatment with Oxysophoridine could effectively downregulate the expression of cytochrome c and caspase-3 in both mRNA and protein levels, and Bax in the protein level, and induce an increase of Bcl-2 in the protein level. The caspase-3, -9, and -8 activities were also inhibited.
CONCLUSIONS:
These findings suggested that Oxysophoridine may be a potential neuroprotective agent for cerebral ischemia injury.

Mol Med Rep. 2015 Jan;11(1):527-32.

Oxysophoridine attenuates the injury caused by acute myocardial infarction in rats through anti-oxidative, anti-inflammatory and anti-apoptotic pathways.[Pubmed: 25338622]

Oxysophoridine (OSR), a natural alkaloid derived from the traditional Chinese medicinal plant sophora alopecuroides, can perform a variety of pharmacological actions. The aim of the present study was to assess the cardioprotective effect of Oxysophoridine against acute myocardial infarction (AMI) in rats.
METHODS AND RESULTS:
Oxysophoridine markedly reduced infarction size and levels of specific myocardial enzymes, including creatine kinase, the MB isoenzyme of creatine kinase, lactate dehydrogenase and cardiac troponin T. A reduced level of malondialdehyde was observed, and elevated catalase, Cu/Zn-superoxide dismutase (SOD), Mn-SOD, non-enzymatic scavenger glutathione and glutathione peroxidase activity were also identified in the Oxysophoridine-treated rats. Additionally, Oxysophoridine inhibited the activities of various inflammatory cytokines in a dose-dependent manner. These included nuclear factor-κB p65, tumor necrosis factor-α, and interleukin-1β, -6 and -10. Furthermore, Oxysophoridine treatment suppressed caspase-3 activity in a dose-dependent manner.
CONCLUSIONS:
These results demonstrate that Oxysophoridine ameliorates cardiac damage in a rat model of AMI and that this cardioprotection may be linked with its anti-oxidative, anti-apoptotic and anti-inflammatory properties.

Neurochem Res. 2013 Nov;38(11):2408-17.

Oxysophoridine protects against focal cerebral ischemic injury by inhibiting oxidative stress and apoptosis in mice.[Pubmed: 24078262]

Our previous studies have demonstrated that Oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation.
METHODS AND RESULTS:
In this study, we further investigated whether Oxysophoridine could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with Oxysophoridine (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. Oxysophoridine pretreatment groups significantly reduced infract volume and neurological deficit scores. Oxysophoridine decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, Oxysophoridine markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of Oxysophoridine (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression.
METHODS AND RESULTS:
These findings indicate that Oxysophoridine has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.

Chin J Integr Med. 2012 Mar;18(3):209-13.

Oxysophoridine suppresses the growth of hepatocellular carcinoma in mice: in vivo and cDNA microarray studies.[Pubmed: 22466946]

To observe the in vivo effects of Oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.
METHODS AND 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.
CONCLUSIONS:
Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma, and its anti-hepatoma effect was probably related to osteoprotegerin activation.

Neural Regen Res. 2013 May 25;8(15):1349-59.

Protective effect of oxysophoridine on cerebral ischemia/reperfusion injury in mice.[Pubmed: 25206429]

Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.