Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury.High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to...Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury.High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma.In this study,we established an oligodendrocyte(OLN-93 cell line)model of ferroptosis induced by RSL-3,an inhibitor of glutathione peroxidase 4(GPX4).RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde.RSL-3 also inhibited the main antiferroptosis pathway,i.e.,SLC7A11/glutathione/glutathione peroxidase 4(xCT/GSH/GPX4),and downregulated acyl-coenzyme A synthetase long chain family member 4.Furthermore,we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis.Liproxstatin-1 was more potent than edaravone or deferoxamine.Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation,but also restored the expression of GSH,GPX4 and ferroptosis suppressor protein 1.These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes,and that liproxstatin-1 is a potent inhibitor of ferroptosis.Therefore,liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.展开更多
Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this...Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress(WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved.Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin(H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot.Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase(GSH-PX), superoxide dismutase(SOD) and catalase(CAT) contents;anti-inflammatory cytokines interleukin-10(IL-10) and prostaglandin E2(PGE2) levels as well as regulatory factors tumor necrosis factor-a(TGF-a) and somatostatin(SS) contents, while decreasing malondialdehyde(MDA), nitric oxide synthase(i NOS), tumor necrosis factor(TNF-a), interleukin-1β(IL-1β), interleukin-6(IL-6), gastrin(GAS)and endothelin(ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen(PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-ΚB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival.Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement展开更多
Luteolin （3＇,4＇,5,7-tetrahydroxyflavone） has powerful anti-apoptotic and antioxidant properties. This study aimed to investigate the effects of luteolin on hyperglycemia-mediated apoptosis in the hippocampi of rat...Luteolin （3＇,4＇,5,7-tetrahydroxyflavone） has powerful anti-apoptotic and antioxidant properties. This study aimed to investigate the effects of luteolin on hyperglycemia-mediated apoptosis in the hippocampi of rats with streptozotocin-induced diabetic encephalopathy after injection into the tail veins, and the molecular mechanisms involved. Biochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling detection results showed that luteolin treatment （given twice daily for 15 days） significantly inhibited hyperglycemia-mediated apoptosis, decreased malondialdehyde levels and increased glutathione levels in the hippocampi of streptozotocin- induced diabetic rats. Western blot analysis revealed that luteolin also inhibited the expression of apoptosis-related factors and cytochrome c release from mitochondria. Luteolin also improved the learning and memory abiJities of rats with diabetic encephalopathy in a water maze test. Further western blot analysis revealed that luteolin treatment facilitated neuronal cell survival through activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, an extracellular signal pathway involved in the suppression of cell apoptosis and promotion of cell survival. These experimental findings indicate that luteolin can inhibit apoptosis of hippocampal nerve cells in rats with diabetic encephalopathy, and that this effect is mediated by an indirect antioxidative effect, the inhibition of activation of apoptosis-related factors and the activation of phosphatidylinositol 3-kinase/Akt signal pathway.展开更多
Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in trea...Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO) II mRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COII mRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81672171(to XY),81972074(to XY),81930070(to SQF),81620108018(to SQF),and 81772342(to GZN)the National Key R&D Program of China,No.2019YFA0112100(to SQF)the Natural Science Foundation of Tianjin of China,No.19JCZDJC34900(to XY)。
文摘Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury.High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma.In this study,we established an oligodendrocyte(OLN-93 cell line)model of ferroptosis induced by RSL-3,an inhibitor of glutathione peroxidase 4(GPX4).RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde.RSL-3 also inhibited the main antiferroptosis pathway,i.e.,SLC7A11/glutathione/glutathione peroxidase 4(xCT/GSH/GPX4),and downregulated acyl-coenzyme A synthetase long chain family member 4.Furthermore,we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis.Liproxstatin-1 was more potent than edaravone or deferoxamine.Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation,but also restored the expression of GSH,GPX4 and ferroptosis suppressor protein 1.These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes,and that liproxstatin-1 is a potent inhibitor of ferroptosis.Therefore,liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.
基金supported by the National Natural Science Foundation of China(No.81673693)the National Key R&D Program of China(No.2017YFD0201402)for financial support.
文摘Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress(WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved.Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin(H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot.Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase(GSH-PX), superoxide dismutase(SOD) and catalase(CAT) contents;anti-inflammatory cytokines interleukin-10(IL-10) and prostaglandin E2(PGE2) levels as well as regulatory factors tumor necrosis factor-a(TGF-a) and somatostatin(SS) contents, while decreasing malondialdehyde(MDA), nitric oxide synthase(i NOS), tumor necrosis factor(TNF-a), interleukin-1β(IL-1β), interleukin-6(IL-6), gastrin(GAS)and endothelin(ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen(PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-ΚB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival.Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement
文摘Luteolin （3＇,4＇,5,7-tetrahydroxyflavone） has powerful anti-apoptotic and antioxidant properties. This study aimed to investigate the effects of luteolin on hyperglycemia-mediated apoptosis in the hippocampi of rats with streptozotocin-induced diabetic encephalopathy after injection into the tail veins, and the molecular mechanisms involved. Biochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling detection results showed that luteolin treatment （given twice daily for 15 days） significantly inhibited hyperglycemia-mediated apoptosis, decreased malondialdehyde levels and increased glutathione levels in the hippocampi of streptozotocin- induced diabetic rats. Western blot analysis revealed that luteolin also inhibited the expression of apoptosis-related factors and cytochrome c release from mitochondria. Luteolin also improved the learning and memory abiJities of rats with diabetic encephalopathy in a water maze test. Further western blot analysis revealed that luteolin treatment facilitated neuronal cell survival through activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, an extracellular signal pathway involved in the suppression of cell apoptosis and promotion of cell survival. These experimental findings indicate that luteolin can inhibit apoptosis of hippocampal nerve cells in rats with diabetic encephalopathy, and that this effect is mediated by an indirect antioxidative effect, the inhibition of activation of apoptosis-related factors and the activation of phosphatidylinositol 3-kinase/Akt signal pathway.
基金This program was supported by National Natural Science Foundation of China (No. 39830450)
文摘Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO) II mRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COII mRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.
