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Acta Pharmaceutica Sinica ; (12): 2127-2133, 2020.
Article in Chinese | WPRIM | ID: wpr-825736


This study was designed to investigate the effect of dihydromyricetin (DHM) on inducing apoptosis of ovarian cancer cells A2780 through endoplasmic reticulum stress (ERS) pathway and the mechanisms involved in vitro and in vivo. A2780 cells were treated with different concentrations of DHM, and the protein expression levels of glucose-regulated protein 78 (GRP78) which is related to ERS increased, apoptotic proteins C/EBP-homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase-12) elevated. After pretreatment with ERS inhibitor, 4-phenyl butyric acid (4-PBA), following the intervention with DHM, the A2780 cell viability decreased and apoptotic rate increased. All animal welfare and experimental procedures were approved by the Animal Ethics Committee of Chongqing Medical University. Intraperitoneal injection of DHM suspension into nude mice with ovarian cancer could significantly inhibit the growth of transplanted tumor in vivo, increase the protein expression levels of GRP78, CHOP, and caspase-3. Moreover, swollen and broken endoplasmic reticulum could be observed in tumor tissues, suggesting that DHM intervention induces apoptosis mediated by ERS. The results indicated that DHM could induce apoptosis of ovarian cancer cells and inhibit the growth of transplanted tumors in nude mice, which might be related to the activation of ERS pathway.

Article in Chinese | WPRIM | ID: wpr-905676


Objective:To explore the effect of trillin on oxidative stress response and nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in rats after spinal cord injury (SCI). Methods:A total of 108 male Sprague-Dawley rats were randomly divided into sham group (n = 36), model group (n = 36) and trillin group (n = 36), each group was divided into one day, three days and seven days subgroups, with twelve rats in each subgroup. The SCI model was established by modified Allen's heavy strike method in the model group and the trillin group, but no obvious injury in the sham group. The trillin group was given trillin 200 mg/kg every day, and the same amount of normal saline was given in the sham group and model group, twice a day. BBB score was performed one day, three days and seven days after modeling. Morphological changes were tested by Nissl's staining, and the changes of malonaldehyde (MDA) content and superoxide dismutase (SOD) activity were detected by ELISA seven days after modeling. The expression of Nrf2, Kelch like ECH associated protein 1 (Keap1), NAD(P)H quinone oxidoreductase (NQO1) and haemoxygenase 1 (HO-1) were detected by Western blotting one day, three days and seven days after modeling. Results:Compared with the model group, BBB scores increased (P < 0.05); the structure of spinal cord was more complete and the number of Nissl bodies increased; SOD activity increased (P < 0.05) and MDA content decreased (P < 0.05); the expression of Nrf2, Keap1, NQO1 and HO-1 increased (P < 0.05) in the trillin group. Conclusion:Trillin may play a protective role in spinal cord injury by inhibiting oxidative stress response and improving the motor function.

Chinese Pharmacological Bulletin ; (12): 1743-1747, 2019.
Article in Chinese | WPRIM | ID: wpr-857082


Aim To explore the effect of Trillium tschonoskii Maxim (TTM) on the expression of miR-NA-155-3p in rats with brain aging induced by D-gal. Methods Fifty SD rats were divided into five groups randomly. The rats were administered with 0. 9% normal saline (NS) subeutaneously every day in control group, 200 mg • kg • d-1 of D-galactose (D-gal) daily inD-galmodelgroup,and50,100and200mg • kg • d-1 of TTM by gavage 2 hours before D-gal injection everyday in TTM treatment groups for 6 weeks. After 5 weeks, Morris water maze was used to test the ability of spatial learning and memory every day. At the 6th week, rats were sacrificed arid hippocampi were tested by Nissl staining and 8-OHdG immunohistochemical (8-OHdC) staining. The expression of miR-155-3p was determined by Real-time PCR, and the levels of Rheb. mTOR, p-inTOR and p70S6K were detected by Western blot. Results The length of escape latency time and path distance in five groups showed a trend of shortening gradually in the orientation navigation experiments. The average escape latency and the distance in D-gal group were longer than those in control group and TTM group (P <0. 01 and 0. 05) , and the number of crossing platform limes less too (P < 0. 05). The arrangement of neurons was irregular and the intercellular space widened in D-gal group compared with those in TTM group by HE staining. There were more Nissl particles in neurons of the hippocampal CA1 area in con-trol group than that in D-gal group, and TTM treatment could increase the number of Nissl bodies-induced by D-gal. Compared with control group, the fluorescence density of 8-OHdG in D-gal group significantly in-creased (P <0. 01) , while that in TTM group was lower than that in D-gal group (P < 0. 05). The expression of miR-155-3p in the hippocampi in D-gal group was significantly higher than that in normal group (P < 0. 05) , while TTM treatment could alleviate D-gal-in-duced increase of miR-155-3p (P < 0. 05) , followed by an increase of the levels of Rheb and p70S6K, and decrease of mTOR. Conclusions The expression of miR-155-3p increased in the hippocampi of aging rats induced by D-gal. TTM could execute the anti-aging process of brain and down-regulate the level of iniR-155-3p through Rheb/mTOR/p70S6K signaling pathway.

Article in Chinese | WPRIM | ID: wpr-850254


Objective To investigate the effect of Trillium tschonoskii Maxim extract on the expression of ciliary neurotrophic factor (CNTF) and its receptor (CNTFRα) after spinal cord injury in rats. Methods Forty-five rats were equally and randomly divided into control group (group A), model group (group B) and Trillium tschonoskii Maxim treated group (group C). Allen's weight drop method was used to reproduce acute spinal cord injury (SCI) model in rats of the group B and C. In group C, the rats were gavaged with Trillium tschonoskii Maxim extract 2 weeks before the injury, while rats in group A and B were fed a same quantity of distilled water.1, 7 or 14 days after injury, the rats were sacrificed to observe the structure of nerve cells after HE and Nissl staining, and the expression of CNTF and CNTFRα with immunohistochemical method, RT-PCR and Western blotting. Results HE staining showed that the structure of spinal cord in the the rats group C was more discernible, with milder edema and necrosis of nerve cells, as compared with that of group B. Nissl staining showed that Nissl bodies were decreased or disappeared in anterior horn motor neurons in both group B and C, but it was significantly less marked in group C than that in group B. Immunohistochemical staining, Western blotting and RT-PCR revealed that the protein and mRNA of CNTF and CNTFRα were positively expressed in rats of every group. The mRNA levels of CNTF and CNTFRα in group C were higher than those in group B. Conclusions Extract of Trillium tschonoskii Maxim can up-regulate the expression of CNTF and CNTFRα, and plays a protective role against injury to spinal cord.

Article in Chinese | WPRIM | ID: wpr-236311


<p><b>OBJECTIVE</b>To explore the effect of Se-riched soybean peptide (SSP) on antioxidant function in rats of fatty liver caused by high-fat diet.</p><p><b>METHODS</b>Forty Wistar rats were divided into 4 groups randomly and fed with standard diet and water (NC), high-fat diet and water (HC), high-fat diet and SSP (0.1 g/d) (SeH), standard diet and SSP (0.1 g/d) (SeN) respectively. After 10 weeks, the rats were killed to investigate the pimelosis level in liver tissues by Sudan III staining and the expression of hepatic GRP78 by immunohistochemical analysis. We also analyzed the changes of liver function, blood lipid, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in livers and serum.</p><p><b>RESULTS</b>The pimelosis level, total cholesterol (TC), triglyceride (TG), MDA contents and the expression of GRP78 in HC group were significantly higher than those in NC, SeN, SeH groups. The activities of GSH-Px and SOD in liver and serum were markedly up-regulated in SeH (P < 0.01). There was no significant difference between NC and SeN groups.</p><p><b>CONCLUSION</b>SSP can improve liver cell injury and the antioxidant functions in rats with fatty liver effectively and decrease the expression of GRP78 in liver.</p>

Animals , Antioxidants , Metabolism , Diet, High-Fat , Disease Models, Animal , Fatty Liver , Metabolism , Heat-Shock Proteins , Metabolism , Liver , Metabolism , Male , Rats , Rats, Wistar , Selenium , Pharmacology , Soybean Proteins , Pharmacology , Soybeans , Chemistry