scholarly journals Scrophularia buergeriana Extract Improves Memory Impairment via Inhibition of the Apoptosis Pathway in the Mouse Hippocampus

2020 ◽  
Vol 10 (22) ◽  
pp. 7987
Author(s):  
Hae Jin Lee ◽  
Dae Young Lee ◽  
Hae Lim Kim ◽  
Seung Hwan Yang
Keyword(s):  
Protein Expression ◽  
Memory Impairment ◽  
Memory Loss ◽  
B Cell Lymphoma ◽  
Beta Amyloid ◽  
Adenosine Diphosphate ◽  
Protective Effects ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Apoptotic Pathways

Scrophularia buergeriana (SB) Miq. (Scrophulariaceae) has been used to help cure swelling and fever and has reported antioxidant and neuro-protective effects. However, few mechanism–based studies have evaluated the memory-improving effects in a beta-amyloid induced memory loss model. As a result of Scrophularia buergeriana extract (SBE) administration (30 and 100 mg/kg) for 28 days significantly recovered beta-amyloid-induced amnesia in the passive avoidance test and improved the impairment of spatial memory in the Morris Water Maze (MWM) task. Furthermore, SBE up-regulated superoxide dismutase-1 (SOD)-1, SOD-2, glutathione peroxidase-1, and B-cell lymphoma (Bcl)-2 protein expression levels. Additionally, SBE downregulated Bcl-2-associated X protein, cleaved caspase-9, cleaved poly (adenosine diphosphate-ribose) polymerase, and Aβ protein expression levels and inhibited the phosphorylation of the tau protein of Aβ-treated mice hippocampus. These results demonstrate that SBE improved memory impairment by reducing beta-amyloid induced neurotoxicity and regulated oxidative stress, anti-apoptotic pathways.

scholarly journals MicroRNA-204-5p regulates apoptosis by targeting Bcl2 in rat ovarian granulosa cells exposed to cadmium†

2020 ◽  
Vol 103 (3) ◽  
pp. 608-619
Author(s):  
Ping Zhong ◽  
Jin Liu ◽  
Hong Li ◽  
Senbin Lin ◽  
Lingfeng Zeng ◽  
...  
Keyword(s):  
Protein Expression ◽  
Granulosa Cells ◽  
B Cell Lymphoma ◽  
Experimental Conditions ◽  
Expression Levels ◽  
Ovarian Granulosa Cells ◽  
Mrna And Protein Expression ◽  
Induced Apoptosis ◽  
Apoptosis Regulation

Abstract This study aimed to investigate whether cadmium (Cd) cytotoxicity in rat ovarian granulosa cells (OGCs) is mediated through apoptosis or autophagy and to determine the role of microRNAs (miRNAs) in Cd cytotoxicity. To test this hypothesis, rat OGCs were exposed to 0, 10, and 20 μM CdCl2 in vitro. As the Cd concentration increased, OGC apoptosis increased. In addition, Cd promoted apoptosis by decreasing the mRNA and protein expression levels of inhibition of B-cell lymphoma 2 (Bcl2). However, under our experimental conditions, no autophagic changes in rat OGCs were observed, and the mRNA and protein expression levels of the autophagic markers microtubule-associated protein 1 light chain 3 alpha (Map1lc3b) and Beclin1 (Becn1) were not changed. Microarray chip analysis, miRNA screening, and bioinformatics approaches were used to further explore the roles of apoptosis regulation-related miRNAs. In total, 19 miRNAs putatively related to Cd-induced apoptosis in rat OGCs were identified. Notably, miR-204-5p, which may target Bcl2, was identified. Then, rat OGCs were cultured in vitro and used to construct the miR-204-5p-knockdown cell line LV2-short hairpin RNA (shRNA). LV2-shRNA cells were exposed to 20 μM Cd for 12 h, and the mRNA and protein expression levels of Bcl2 were increased. Our findings suggest that Cd is cytotoxic to rat OGCs, and mitochondrial apoptosis rather than autophagy mediates Cd-induced damage to OGCs. Cd also affects apoptosis-related miRNAs, and the underlying apoptotic mechanism may involve the Bcl2 gene.

scholarly journals Yiqi Huoxue Recipe Improves Liver Regeneration in Rats after Partial Hepatectomy via JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wen-cong Li ◽  
Su-xian Zhao ◽  
Wei-guang Ren ◽  
Hui-juan Du ◽  
Yu-guo Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Protective Effects ◽  
Jnk Pathway ◽  
Expression Levels ◽  
Protein Levels ◽  
Mrna And Protein Expression

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.

scholarly journals Protective Effects of Tao-Hong-Si-Wu Decoction on Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Lan Han ◽  
Zhaojie Ji ◽  
Weidong Chen ◽  
Dengke Yin ◽  
Fan Xu ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Memory Impairment ◽  
B Cell Lymphoma ◽  
Artery Occlusion ◽  
Hippocampal Damage ◽  
Neural Cells ◽  
Protective Effects ◽  
Thrombotic Diseases ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

Tao-Hong-Si-Wu decoction (TSD) as a traditional chinese medicine (TCM) has been developed to treat thrombotic diseases for hundreds of years, and vascular dementia (VD) is a cognitive dysfunction syndrome caused by cerebral embolism. In this study, the protective effect of TSD on memory impairment and brain damage in rat model of VD induced by middle cerebral artery occlusion (MCAO) was investigated. The study showed that rats in MCAO treatment with TSD for 14 days significantly improved behavioral function, increased densities of neuron, and induced angiogenesis in the brain compared with model rats. TSD also adjusted the neurotransmitter levels, reduced the content of endothelin-1 (ET-1), and induced the activities of vascular endothelial growth factor (VEGF) in hippocampus. Moreover, the immunohistochemical staining and western blotting results also revealed that TSD decreased apoptosis via upregulated B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio. These results demonstrated TSD possesses neuroprotective and antidementia properties by preventing the loss of neural cells, adjusting brain neurotransmitter, promoting cerebral blood circulation, and decreasing apoptosis. These results suggested that TSD might be developed as an effective drug for the prevention of VD.

Coexpression of MYC and BCL-2 Predicts Inferior Survival in Pgi-DLBCL Treated with CHOP-like Regimen/Rituximab

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5404-5404 ◽  
Author(s):  
Le Zhang ◽  
Bing Xia ◽  
Shanqi Guo ◽  
Xiaowu Li ◽  
Fulian Qu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Chemotherapy Response ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Expression Levels ◽  
Stage Disease

Abstract MYC protein expression has been identified to be associated with inferior overall survival (OS) and progression-free survival (PFS) when coexpressed with BCL-2 protein in patients with diffuse large B cell lymphoma (DLBCL). But the concurrent expression of MYC and BCL-2 proteins in primary gastrointestinal (PGI)-DLBCL has not been clearly understood. Here, we investigated whether this coexpression has prognostic significance in PGI-DLBCL patients and explored its associations with patients’ clinical parameters. We enrolled 60 PGI-DLBCL patients and 30 age- and sex-matched healthy controls. Expression levels of MYC and BCL-2 were detected from both protein and mRNA levels by immunohistochemistry and real-time RT-PCR. Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein were correlated with high MYC and BCL-2 mRNA expression, respectively (both p<0.05). We found that patients with advanced-stage disease (at IIE-IV) having higher MYC and BCL-2 coexpression levels (p<0.05). In addition, MYC+/BCL-2+ patients had more difficulty achieving complete remission than others (p<0.05). Presence of MYC protein expression only affected OS and PFS when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (p<0.05) even after adjusting for age, Lugano stage, IPI, and BCL-2 protein expression in a multivariable model. MYC+/BCL-2+ patients have poorer chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting prognosis of PGI-DLBCL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Small-molecule XIAP antagonist restores caspase-9–mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 369-375 ◽  
Author(s):  
Saskia A. G. M. Cillessen ◽  
John C. Reed ◽  
Kate Welsh ◽  
Clemencia Pinilla ◽  
Richard Houghten ◽  
...  
Keyword(s):  
B Cell ◽  
Small Molecule ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Caspase 9 ◽  
Lymphoma Cells ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Apoptosis Protein ◽  
Large B Cell

Clinical outcome in patients with primary nodal diffuse large B-cell lymphomas (DLBCLs) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including X-linked inhibitor of apoptosis protein (XIAP). XIAP suppresses apoptosis through inhibiting active caspase-3, caspase-7, and caspase-9. In this study, we investigated to see if the small-molecule XIAP antagonist 1396-12 induces cell death in cultured lymphoma cells of patients with DLBCL. Treatment with this XIAP antagonist resulted in relief of caspase-3 inhibition and in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy-refractory and -responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal-center B cells from healthy donors. XIAP antagonist-sensitive samples were characterized by high expression levels of XIAP, relatively low expression levels of Bcl-2, and by constitutive caspase-9 activation. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in cultured DLBCL cells and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers, suggesting the possibility of predefining patients most likely to benefit from XIAP antagonist therapy.

scholarly journals Scrophularia buergeriana Extract (Brainon) Improves Scopolamine-Induced Neuronal Impairment and Cholinergic Dysfunction in Mice through CREB-BDNF Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 4286
Author(s):  
Hae-Jin Lee ◽  
Hae-Lim Kim ◽  
Dae-Young Lee ◽  
Dong-Ryung Lee ◽  
Bong-Keun Choi ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Avoidance Performance ◽  
Memory Loss ◽  
Adenosine Diphosphate ◽  
Acetylcholinesterase Activity ◽  
Camp Response Element Binding ◽  
Mrna Levels ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
Apoptotic Effects

We evaluated the effectiveness of Scrophularia buergeriana extract (Brainon) on cognitive dysfunction and determined its underlying mechanisms in a scopolamine (SCO)-treated mouse model of memory impairment. Brainon treatment for 28 days ameliorated the symptoms of memory impairment as indicated by the results of both passive avoidance performance and the Morris water mazes. Brainon lowered acetylcholinesterase activity and raised acetylcholine levels in the hippocampus. The treatment elevated the protein levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding (CREB). Additionally, the excessive generation of SCO-induced reactive oxygen species (ROS) and subsequent oxidative stress were suppressed by the enhancement of superoxide dismutase (SOD)-1 and SOD-2 proteins. mRNA levels of upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, as well as the apoptotic protein Bcl-2-associated X protein (Bax), cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase (PARP) expression after SCO injection were downregulated by Brainon treatment. Collectively, these findings suggested that Brainon possesses anti-amnesic effects through the CREB-BDNF pathway. Moreover, it exerted antioxidant, anti-inflammatory, and anti-apoptotic effects in SCO-induced mice exhibiting cognitive impairment and memory loss.

scholarly journals Protective Effects of Colivelin Against Alzheimer's Disease in a PDAPP Mouse Model

2016 ◽  
Vol 38 (3) ◽  
pp. 1138-1146 ◽  
Author(s):  
Rong Yin ◽  
Kai Yin ◽  
ZhiQiang Guo ◽  
ZhiQiang Zhang ◽  
LiPin Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Memory Loss ◽  
The Elderly ◽  
Morris Water Maze Test ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Western Blot Assay ◽  
P38 Inhibitor

Background: Alzheimer's disease (AD) is characterized with progressive memory loss and severe cognitive impairments, which affect everyday life and human health in the elderly. It is required that an effective and safe protective reagent against AD should be developed. It has been reported that humanin (HN) exerts neuroprotective effects against AD. In this study, we investigated the effect of a novel and more effective HN derivative, Colivelin (CLN) on AD. Methods: PDAPPV717I transgenic AD model mice (derived from parental C57/BL6 mice) were used in our study as AD model. Morris water maze test was used to test the memory impairment of AD mice and the levels of Aβ40 and Aβ42 were determined by an Elisa assay. We used an Immunohistochemistry and Immunofluorescence staining method to check the GFAP and MAP2 positive cells, and TUNEL to assess the apoptotic cells. Western blot assay was used to check the expression and phosphorylation level of p38. Results: We found that CLN improved the memory impairment induced by AD and reduced the deposit of Aβ40 and Aβ42. CLN also inhibited cell apoptosis and activation of caspase 3 in brain tissues of AD mice. Inflammation in AD mice was alleviated by CLN treatment, including the accumulation of GFAP positive cells and the inflammatory cytokines. With both structure of AGA-HNG and ANDF, CLN exhibited significantly stronger effects than synchronously administration of AGA-HNG and ADNF, suggesting CLN as a novel potential effective therapeutic reagent for AD patients. Finally, we found that CLN inhibited phosphorylation of p38 in AD mice and p38 inhibitor, SB203580 weakened the therapeutic effect of CLN. Conclusion: CLN effectively improved the memory dysfunction in PDAPP mice, and our data suggests CLN as a novel and effective reagent which may have great potentials in AD therapy.

Small-Molecule XIAP Antagonist Restores Caspase-9-Mediated Apoptosis in XIAP-Positive Diffuse Large B-Cell Lymphoma Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 803-803 ◽  
Author(s):  
Saskia A.G.M. Cillessen ◽  
John C. Reed ◽  
Clemencia Pinilla ◽  
Chris J.L.M. Meijer ◽  
Erik Hooijberg ◽  
...  
Keyword(s):  
B Cell ◽  
Small Molecule ◽  
Mononuclear Cells ◽  
B Cell Lymphoma ◽  
Caspase 9 ◽  
Lymphoma Cells ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Intrinsic Apoptosis Pathway ◽  
Large B Cell

Abstract Clinical outcome in patients with diffuse large B-cell lymphomas (DLBCL) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including XIAP. XIAP suppresses apoptosis through inhibiting active caspases-3, -7 and -9. In this study we investigated if the small-molecule XIAP antagonist 1396–12 induces cell death in cultured lymphoma cells of DLBCL patients and whether it is possible to predict whether a DLBCL will be sensitive to the XIAP antagonist. Treatment with this XIAP antagonist resulted in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy refractory and responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal center B-cells from healthy donors. XIAP antagonist-sensitive cases were characterized by high expression levels of XIAP and relatively low expression levels of Bcl-2. In addition, we found that XIAP antagonist sensitive lymphomas are characterized by constitutive caspase-9 activation and that the apoptosis inducing effect of the XIAP antagonist depends on this constitutive caspase 9 activity. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in DLBCL cells by restoring caspase 9 mediated apoptosis and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers suggesting the possibility of pre-defining patients most likely to benefit from XIAP antagonist therapy.

scholarly journals Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Huan Liu ◽  
Hongrui Guo ◽  
Zhijie Jian ◽  
Hengmin Cui ◽  
Jing Fang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Mouse Liver ◽  
B Cell Lymphoma ◽  
Death Domain ◽  
Expression Levels ◽  
Mrna And Protein Expression ◽  
High Doses ◽  
Induced Apoptosis

Copper (Cu) is an essential trace element involved in the normal physiological processes of animals. However, excessive exposure to Cu can produce numerous detrimental impacts. The aim of this study was to investigate the effects of Cu on oxidative stress and apoptosis as well as their relationship in the mouse liver. Four-week-old ICR mice (n=240) were randomly assigned to different Cu (Cu2+-CuSO4) treatment groups (0, 4, 8, and 16 mg/kg) for periods of 21 and 42 days. The high doses of Cu exposure could induce oxidative stress, by increasing the levels of reactive oxygen species (ROS) and protein carbonyls (PC) and decreasing the activities of antisuperoxide anion (ASA) and antihydroxyl radical (AHR) and content of glutathione (GSH), as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Moreover, high doses of Cu exposure induced hepatic apoptosis via the mitochondrial apoptotic pathway, as characterized by the depolarization of mitochondrial membrane potential (MMP); significantly increased mRNA and protein expression levels of cytosolic cytochrome (Cyt c), apoptosis-inducing factor (AIF), endonuclease G (Endo G), apoptosis protease-activating factor-1 (Apaf-1), cleaved caspase-9, cleaved caspase-3, cleaved PARP, Bcl-2 antagonist killer (Bak), Bcl-2-associated X protein (Bax), and Bcl-2-interacting mediator of cell death (Bim); and decreased mRNA and protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-extra-large (Bcl-xL). Furthermore, the activation of the tumor necrosis factor receptor-1 (TNF-R1) signaling pathway was involved in Cu-induced apoptosis, as characterized by the significantly increased mRNA and protein expression levels of TNF-R1, Fas-associated death domain (FADD), TNFR-associated death domain (TRADD), and cleaved caspase-8. These results indicated that exposure to excess Cu could cause oxidative stress triggered by ROS overproduction and diminished antioxidant function, which in turn promoted hepatic apoptosis via mitochondrial apoptosis and that the TNF-R1 signaling pathway was also involved in the Cu-induced apoptosis.

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