AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 β and interferon-γ-mediated β cell death and abolition of insulin secretion....AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 β and interferon-γ-mediated β cell death and abolition of insulin secretion. METHODS: By employing BRIN-BD11 cells, the effects of SA-Et administration on cytokine-mediated cell death and abolition of insulin secretion were evaluated by a viability assay, cell cycle analysis, and insulin assay. The associated gene and protein expressions were also measured. In addition, the bioactivities of several peak compounds collected from the SA-Et were tested against cytokine-mediated β cell death.RESULTS: Our Results revealed that SA-Et dose-dependently ameliorated cytokine-mediated β cell death and apoptosis. Instead of suppressing inducible nitric oxide synthase/nitric oxide cascade or p38MAPK activity, suppression of stress-activated protein kinase/c-Jun NH2-terminal kinase activity appeared to be the target for SA-Et against the cytokine mix. In addition, SA-Et provided some insulinotropic effects which re-activated the abolished insulin exocytosis in cytokine-treated BRIN-BD11 cells. Finally, schiarisanrin A and B isolated from the SA-Et showed a dose-dependent protective effect against cytokine-mediated β cell death. CONCLUSION: This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.展开更多
Background We previously demonstrated that the aqueous extract of the Schizandra chinensis fruit （AESC） ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity.In th...Background We previously demonstrated that the aqueous extract of the Schizandra chinensis fruit （AESC） ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity.In the present study,we investigated the effect of AESC on anxiety-like behavior and the levels of norepinephrine and 3-methoxy-4-hydroxyphenylglycol （a metabolite of norepinephrine） in different brain regions during ethanol withdrawal in rats.Methods Male Sprague-Dawley rats were treated with 3 g/kg of ethanol （20％,w/v） or saline by daily intraperitoneal injection for 28 days followed by three days of withdrawal.During withdrawal,rats were given AESC （100 mg.kg 1.d-1 or 300 mg.kg 1·d1,P.O.） once a day for three days.Thirty minutes after the final dose of AESC,the anxiogenic response was evaluated using an elevated plus maze,and the plasma corticosterone levels were examined by radioimmunoassay.Meanwhile,the concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol in the hypothalamic paraventricular nucleus and hippocampus were also measured by high performance liquid chromatography.Results Rats undergoing ethanol withdrawal exhibited substantial anxiety-like behavior,which was characterized by both the decrease in time spent in the open arms of the elevated plus maze and the increased level of corticosterone secretion,which were greatly attenuated by doses of AESC in a dose-dependent manner.The high performance liquid chromatography analysis revealed that ethanol withdrawal significantly increased norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the hypothalamic paraventricular nucleus,while not significantly altering them in the hippocampus.Similar to the results from the elevated plus maze test,the AESC significantly inhibited the elevation of norepinephrine and its metabolite in the hypothalamic paraventricular nucleus in a dose-dependent manner.Conclusions These results suggest that AESC attenuates anxiety-like behavior induced by ethanol withdrawal through modulation of the hypothalamic norepinephrine system in the brain.展开更多
基金Supported by National Science Council, No. NSC94-2314-B-077-001, No. NSC101-2320-B-077-003-MY2National Research Institute of Chinese Medicine, No. NRICM95-DHM-04
文摘AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 β and interferon-γ-mediated β cell death and abolition of insulin secretion. METHODS: By employing BRIN-BD11 cells, the effects of SA-Et administration on cytokine-mediated cell death and abolition of insulin secretion were evaluated by a viability assay, cell cycle analysis, and insulin assay. The associated gene and protein expressions were also measured. In addition, the bioactivities of several peak compounds collected from the SA-Et were tested against cytokine-mediated β cell death.RESULTS: Our Results revealed that SA-Et dose-dependently ameliorated cytokine-mediated β cell death and apoptosis. Instead of suppressing inducible nitric oxide synthase/nitric oxide cascade or p38MAPK activity, suppression of stress-activated protein kinase/c-Jun NH2-terminal kinase activity appeared to be the target for SA-Et against the cytokine mix. In addition, SA-Et provided some insulinotropic effects which re-activated the abolished insulin exocytosis in cytokine-treated BRIN-BD11 cells. Finally, schiarisanrin A and B isolated from the SA-Et showed a dose-dependent protective effect against cytokine-mediated β cell death. CONCLUSION: This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.
文摘Background We previously demonstrated that the aqueous extract of the Schizandra chinensis fruit （AESC） ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity.In the present study,we investigated the effect of AESC on anxiety-like behavior and the levels of norepinephrine and 3-methoxy-4-hydroxyphenylglycol （a metabolite of norepinephrine） in different brain regions during ethanol withdrawal in rats.Methods Male Sprague-Dawley rats were treated with 3 g/kg of ethanol （20％,w/v） or saline by daily intraperitoneal injection for 28 days followed by three days of withdrawal.During withdrawal,rats were given AESC （100 mg.kg 1.d-1 or 300 mg.kg 1·d1,P.O.） once a day for three days.Thirty minutes after the final dose of AESC,the anxiogenic response was evaluated using an elevated plus maze,and the plasma corticosterone levels were examined by radioimmunoassay.Meanwhile,the concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol in the hypothalamic paraventricular nucleus and hippocampus were also measured by high performance liquid chromatography.Results Rats undergoing ethanol withdrawal exhibited substantial anxiety-like behavior,which was characterized by both the decrease in time spent in the open arms of the elevated plus maze and the increased level of corticosterone secretion,which were greatly attenuated by doses of AESC in a dose-dependent manner.The high performance liquid chromatography analysis revealed that ethanol withdrawal significantly increased norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the hypothalamic paraventricular nucleus,while not significantly altering them in the hippocampus.Similar to the results from the elevated plus maze test,the AESC significantly inhibited the elevation of norepinephrine and its metabolite in the hypothalamic paraventricular nucleus in a dose-dependent manner.Conclusions These results suggest that AESC attenuates anxiety-like behavior induced by ethanol withdrawal through modulation of the hypothalamic norepinephrine system in the brain.
