BACKGROUND Based on current knowledge,hepatocellular carcinoma(HCC)is a condition with numerous etiologies and risk factors.However,the pathogenesis of HCC remains unclear.AIM To investigate the roles of senegenin and...BACKGROUND Based on current knowledge,hepatocellular carcinoma(HCC)is a condition with numerous etiologies and risk factors.However,the pathogenesis of HCC remains unclear.AIM To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of HCC.METHODS The levels of O-linked N-acetylglucosamine transferase(OGT)and O-GlcNAcylation in HCC cells and tissues were detected using western blot analysis.The effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic assays.The potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay.O-GlcNAcylation levels were altered via drug treatment and lentiviral infection,and western blot analysis was used to detect proteins involved in various pathways.RESULTS Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells.O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral infection.An increase in the glycosylation level was linked to enhanced proliferation,invasiveness,clonogenicity,and metastatic potential of cancer cells.O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC cells.The levels of proteins involved in nuclear factor-kappa B(NF-κB)and c-Jun N-terminal kinase(JNK)pathways,which are associated with endoplasmic reticulum stress,were altered.CONCLUSION Senegenin lowers O-GlcNAcylation levels,decreases OGT expression,and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.展开更多
Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus. However, the effects of senegenin on mesencephalon-deriv...Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus. However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood. Cells from a ventral mesencephalon neural progenitor cell line （ReNcell VM） were utilized as models for pharmaceutical screening. The effects of various senegenin concentrations on cell proliferation were analyzed, demonstrating that high senegenin concentrations （5, 10, 50, and 100 μmol/L）, particularly 50 μmol/L, significantly promoted proliferation of ReNcell VM cells. In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases. Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors. Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.展开更多
Senegenin has been shown to inhibit neuronal apoptosis,thereby exerting a neuroprotective effect.In the present study,we established a rat model of spinal cord contusion injury using the modified Allen＇s method.Three...Senegenin has been shown to inhibit neuronal apoptosis,thereby exerting a neuroprotective effect.In the present study,we established a rat model of spinal cord contusion injury using the modified Allen＇s method.Three hours after injury,senegenin（30 mg/g） was injected into the tail vein for 3 consecutive days.Senegenin reduced the size of syringomyelic cavities,and it substantially reduced the number of apoptotic cells in the spinal cord.At the site of injury,Bax and Caspase-3 m RNA and protein levels were decreased by senegenin,while Bcl-2 m RNA and protein levels were increased.Nerve fiber density was increased in the spinal cord proximal to the brain,and hindlimb motor function and electrophysiological properties of rat hindlimb were improved.Taken together,our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury.展开更多
Objective： To investigate the effect and the potential mechanism of Senegenin （Sen） against injury induced by hypoxia/reoxygenation （H/R） in highly differentiated PC12 cells. Methods： The cultured PC12 cells wer...Objective： To investigate the effect and the potential mechanism of Senegenin （Sen） against injury induced by hypoxia/reoxygenation （H/R） in highly differentiated PC12 cells. Methods： The cultured PC12 cells were treated with H/R in the presence or absence of Sen （60 μmol/L）. Four groups were included in the experiment： control group, H/R group, H/R＋Sen group and Sen group. Cell viability of each group and the level of lactate dehydrogenase （LDH） in culture medium were detected for the pharmacological effect of Sen. Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate. Moreover, mitochondrial membrane potential （△ψm）, reactive oxygen species （ROS） and intracellular free calcium （[Ca2＋]i） were measured by fluorescent staining and flow cytometry. Cleaved caspase-3 and activity of NADPH oxidase （NOX） were determined by colorimetric protease assay and enzyme linked immunosorbent assay, respectively. Results： Sen significantly elevated cell viability （P〈0.05）, decreased the leakage of LDH （P〈0.05） and apoptosis rate （P〈0.05） in H/R-injured PC12 cells. Sen maintained the value of △ψm （P〈0.05） and suppressed the activity of caspase-3 （P〈0.05）. Moreover, Sen reduced ROS accumulation （P〈0.05） and [Ca2＋]i increment （P〈0.05） by inhibiting the activity of NOX （P〈0.05）. Conclusion： Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and [Ca2＊]~, thereby suppressing the mitochondrial pathway of cellular apoptosis.展开更多
文摘BACKGROUND Based on current knowledge,hepatocellular carcinoma(HCC)is a condition with numerous etiologies and risk factors.However,the pathogenesis of HCC remains unclear.AIM To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of HCC.METHODS The levels of O-linked N-acetylglucosamine transferase(OGT)and O-GlcNAcylation in HCC cells and tissues were detected using western blot analysis.The effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic assays.The potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay.O-GlcNAcylation levels were altered via drug treatment and lentiviral infection,and western blot analysis was used to detect proteins involved in various pathways.RESULTS Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells.O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral infection.An increase in the glycosylation level was linked to enhanced proliferation,invasiveness,clonogenicity,and metastatic potential of cancer cells.O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC cells.The levels of proteins involved in nuclear factor-kappa B(NF-κB)and c-Jun N-terminal kinase(JNK)pathways,which are associated with endoplasmic reticulum stress,were altered.CONCLUSION Senegenin lowers O-GlcNAcylation levels,decreases OGT expression,and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.
基金the National Basic Research Program of China-973 Project,No. 2006CB500700the National Natural Science Foundation of China,No. 30500255the Natural Science Foundation of Beijing,No. 5102010
文摘Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus. However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood. Cells from a ventral mesencephalon neural progenitor cell line （ReNcell VM） were utilized as models for pharmaceutical screening. The effects of various senegenin concentrations on cell proliferation were analyzed, demonstrating that high senegenin concentrations （5, 10, 50, and 100 μmol/L）, particularly 50 μmol/L, significantly promoted proliferation of ReNcell VM cells. In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases. Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors. Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.
基金supported by a grant from the Science and Technology Development Plan of Jilin Province of China,No.2011084
文摘Senegenin has been shown to inhibit neuronal apoptosis,thereby exerting a neuroprotective effect.In the present study,we established a rat model of spinal cord contusion injury using the modified Allen＇s method.Three hours after injury,senegenin（30 mg/g） was injected into the tail vein for 3 consecutive days.Senegenin reduced the size of syringomyelic cavities,and it substantially reduced the number of apoptotic cells in the spinal cord.At the site of injury,Bax and Caspase-3 m RNA and protein levels were decreased by senegenin,while Bcl-2 m RNA and protein levels were increased.Nerve fiber density was increased in the spinal cord proximal to the brain,and hindlimb motor function and electrophysiological properties of rat hindlimb were improved.Taken together,our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury.
基金Supported by the Natural Science Foundation of Guangdong Province,China(No.2014A030313394)the Project of Science and Technology of Guangzhou,China(No.2014J4100098)+1 种基金the National Program on Key Basic Research Project(973 Program,No.2011CB707501)the Fundamental Research Funds for the Central Universities in China(No.21613401)
文摘Objective： To investigate the effect and the potential mechanism of Senegenin （Sen） against injury induced by hypoxia/reoxygenation （H/R） in highly differentiated PC12 cells. Methods： The cultured PC12 cells were treated with H/R in the presence or absence of Sen （60 μmol/L）. Four groups were included in the experiment： control group, H/R group, H/R＋Sen group and Sen group. Cell viability of each group and the level of lactate dehydrogenase （LDH） in culture medium were detected for the pharmacological effect of Sen. Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate. Moreover, mitochondrial membrane potential （△ψm）, reactive oxygen species （ROS） and intracellular free calcium （[Ca2＋]i） were measured by fluorescent staining and flow cytometry. Cleaved caspase-3 and activity of NADPH oxidase （NOX） were determined by colorimetric protease assay and enzyme linked immunosorbent assay, respectively. Results： Sen significantly elevated cell viability （P〈0.05）, decreased the leakage of LDH （P〈0.05） and apoptosis rate （P〈0.05） in H/R-injured PC12 cells. Sen maintained the value of △ψm （P〈0.05） and suppressed the activity of caspase-3 （P〈0.05）. Moreover, Sen reduced ROS accumulation （P〈0.05） and [Ca2＋]i increment （P〈0.05） by inhibiting the activity of NOX （P〈0.05）. Conclusion： Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and [Ca2＊]~, thereby suppressing the mitochondrial pathway of cellular apoptosis.
