Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

Aim. To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms. Methods. A total of 48 healthy male SD rats were randomly divided into control group, AD model group, resveratrol group, and crocin group, with 12 rats per group. AD model was established by injecting Aβ25–35 to the lateral ventricle of rats, and thereafter the rats were administrated with resveratrol (40 mg/kg), crocin (40 mg/kg), or PBS daily for 14 days. Y-maze test and sucrose preference test were used to detect the learning and memory acquisition of rats. Neuronal apoptosis was detected by TUNEL staining and Western blot for apoptosis-related proteins Bax, Bcl-2, and Caspase-3. Immunofluorescence staining and Western blot tests were used to detect the expression of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hippocampal CA1 region (Hippo) and prefrontal cortical neurons (PFC). Results. The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (P<0.01), while resveratrol and crocin significantly decreased the apoptotic cell number in AD group (P<0.01). Compared with the control group, the expression of Bcl2 in PFC and hippo of AD model group was significantly decreased (P<0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased (P<0.01). Resveratrol and crocin could significantly reverse the expression of these proteins in AD rats (P<0.05). Conclusion. Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.

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Sodium Citrate Inhibits Endoplasmic Reticulum Stress in Rats with Adenine-Induced Chronic Renal Failure

American Journal of Nephrology ◽

10.1159/000437235 ◽

2015 ◽

Vol 42 (1) ◽

pp. 14-21 ◽

Cited By ~ 9

Author(s):

Yan Ou ◽

Wenqian Hou ◽

Shuiqin Li ◽

Xiaojing Zhu ◽

Yan Lin ◽

...

Keyword(s):

Renal Failure ◽

Endoplasmic Reticulum ◽

Chronic Renal Failure ◽

Endoplasmic Reticulum Stress ◽

Western Blot ◽

Low Dose ◽

Sodium Citrate ◽

Control Group ◽

High Dose ◽

Model Group

Background/Aims: Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli that contribute to various diseases, including chronic renal failure (CRF). Sodium citrate plays an important role in antioxidant and cellular immunity, but whether it improves ERS in CRF is unclear. Methods: The rats were randomly divided into five groups: the control group, the sodium citrate control group, the model group, model rats with low dose sodium citrate (216 mg/kg), and model rats with a high dose of sodium citrate (746 mg/kg). The rats were euthanized at 6, 8, 12, and 16 weeks with their blood and renal tissue in detection. Results: The increased concentrations of blood urea nitrogen and serum creatinine in the model group were significantly decreased by sodium citrate treatment. Hematoxylin-eosin and Masson staining showed that sodium citrate treatment apparently improved renal pathological changes in CRF rats. Western blot analysis showed that sodium citrate treatment decreased the protein levels of transforming growth factor-beta 1 and collagen type IV, which were increased in model rats. Moreover, immunohistochemical staining demonstrated that sodium citrate could effectively reduce the protein expression of glucose-regulated protein 78 kDa and CCAAT/enhancer-binding protein homologous protein in the model rats, which was consistent with western blot results. Additionally, the high dose of sodium citrate had a stronger protective effect in CRF rats than the low dose of sodium citrate. Conclusions: Sodium citrate has a protective effect on CRF through its effects on ERS.

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Effect of Pioglitazone on endoplasmic reticulum stress regarding in situ perfusion rat model

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211163 ◽

2021 ◽

pp. 1-15

Author(s):

Vivien Telek ◽

Luca Erlitz ◽

Ibitamuno Caleb ◽

Tibor Nagy ◽

Mónika Vecsernyés ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Western Blot ◽

Rat Model ◽

Ischemia Reperfusion ◽

Effective Dosage ◽

Control Group ◽

Histopathological Changes ◽

In Situ Perfusion

BACKGROUND: Ischemia-reperfusion injury (IRI) can cause insufficient microcirculation of the transplanted organ and results in a diminished and inferior graft survival rate. OBJECTIVE: This study aimed to investigate the effect of different doses of an anti-diabetic drug, Pioglitazone (Pio), on endoplasmic reticulum stress and histopathological changes, using an in situ perfusion rat model. METHODS: Sixty male Wistar rats were used and were divided into six groups, consisting of the control group, vehicle-treated group and four Pio-treated groups (10, 20, 30 and 40 mg/kg Pio was administered). The rats were perfused through vena cava and an outflow on the abdominal aorta occurred. Following the experiment, kidneys and livers were collected. The level of the endoplasmic reticulum stress markers (XBP1 and Caspase 12) was analyzed using Western blot and histopathological changes were evaluated. RESULTS: Histopathological findings were correlated with the Western blot results and depict a protective effect corresponding to the elevated dosage of Pioglitazone regarding in situ perfusion rat model. CONCLUSIONS: In our study, Pioglitazone can reduce the endoplasmic reticulum stress, and the most effective dosage proved to be the 40 mg/kg Pio referencing the kidney and liver samples.

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Dexmedetomidine protects human renal tubular epithelial HK-2 cells against hypoxia/reoxygenation injury by inactivating endoplasmic reticulum stress pathway

10.21203/rs.2.17940/v1 ◽

2019 ◽

Author(s):

Mingyu Zhai ◽

Mingming Han ◽

Xiang Huang ◽

Fang Kang ◽

Chengwei Yang ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Western Blot ◽

Cell Viability ◽

Cell Apoptosis ◽

Caspase 3 ◽

Control Group ◽

Sod Activity ◽

Renal Tubular ◽

Hypoxia Reoxygenation

Abstract Background: The study was aimed to explore the effects and potential mechanisms of Dexmedetomidine (Dex) on hypoxia/reoxygenation (H/R) injury in human renal tubular epithelial HK-2 cells. Methods: Human renal tubular epithelial HK-2 cells were divided into four groups: control group, Dex group, H/R group, and Dex + H/R group. After treatment, cell viability rate and cell apoptosis rate were measured by MTT assay and flow cytometry, respectively. Afterwards, the expressions of Hypoxia-inducible factor 1 (HIF-1α), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12 and cleaved caspase-3 were determined by western blot. Malondialdehyde (MDA) concentration and Superoxide Dismutase (SOD) activity were determined by assay kits. Results: Compared with control group, the cell viability rate was decreased and cell apoptotic was increased in H/R group. Besides, cell viability rate was increased, and cell apoptotic rate of HK-2 cells was decreased in Dex + H/R group, compared with H/R group. Western blot analysis showed that the expression of HIF-1α was up-regulated, and the expressions of GRP78, CHOP, capase-12 and cleaved caspase-3 were down-regulated in Dex + H/R group. In addition, the concentrations of MDA in Dex + H/R group and H/R group were 1.68 ± 0.22 nmol/mgprot and 0.85 ± 0.16 nmol/mgprot, which showed a 49.4% decrease in Dex + H/R group. However, after Dex treatment, the SOD activity was rose to 121 ± 11 U/L, which was more than twice larger than that in H/R group (57 ± 10 U/L). Conclusions: Dex could inhibit cell apoptosis by up-regulating the expression of HIF-1α, reducing endoplasmic reticulum stress and regulating oxidative stress, thus ameliorating the H/R injury.

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