Qiangji Decoction Alleviates Neurodegenerative Changes and Hippocampal Neuron Apoptosis Induced by D-Galactose via Regulating AMPK/SIRT1/NF-κB Signaling Pathway

Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.

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Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats withAβ1–40-Induced Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/942917 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Hai-yan Hu ◽

Zhi-hui Cui ◽

Hui-qin Li ◽

Yi-ru Wang ◽

Xiang Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Signaling Pathway ◽

Learning And Memory ◽

Ming Dynasty ◽

Neuronal Apoptosis ◽

Caspase 3 ◽

Tunel Staining ◽

Apoptotic Signaling ◽

Chinese Herbal

Alzheimer’s disease (AD) is the most common form of dementia and lacks disease-altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal prescription for dementia, was first recorded in theComplete Works of Jingyueduring the Ming Dynasty. This study aimed to investigate whether FMJ could prevent cognitive deficit and take neuroprotective effects inAβ1–40-induced rat model through apoptotic signaling pathway. AD model was established by bilateral injection ofAβ1–40into hippocampus in rat. All rats were tested for their capabilities of spatial navigation and memorization by Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT-PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein level of cleaved caspase-3. After 14 days of treatment, FMJ significantly improved the escape latency and enhanced platform-cross number compared with theAβ1–40-injected group (P<0.05orP<0.01). FMJ also significantly decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax and cleaved Caspase-3 and increased the expression of Bcl-2 (P<0.01) compared with AD model group. In conclusion, FMJ exerts a protective effect againstAβ1–40-induced learning and memory deficits and neuronal apoptosis, suggesting that FMJ could be used as a potential therapeutic formula for AD.

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Elaeagnus glabra f. oxyphylla Attenuates Scopolamine-Induced Learning and Memory Impairments in Mice by Improving Cholinergic Transmission via Activation of CREB/NGF Signaling

Nutrients ◽

10.3390/nu11061205 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1205 ◽

Cited By ~ 2

Author(s):

Eunjin Sohn ◽

Hye-Sun Lim ◽

Yu Jin Kim ◽

Bu-Yeo Kim ◽

Joo-Hwan Kim ◽

...

Keyword(s):

Learning And Memory ◽

Ethanol Extract ◽

Treated Group ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Tunel Staining ◽

Therapeutic Effects ◽

Memory Impairments ◽

Group A ◽

Ngf Signaling

We aimed to investigate the therapeutic effects of an Elaeagnus glabra f. oxyphylla (EGFO) ethanol extract in mice with scopolamine-induced memory dysfunction. Fifty male mice were randomly divided into a normal control group, a scopolamine-treated group, a scopolamine and EGFO extract-treated group, and a scopolamine and tacrine-treated group. EGFO (50 or 100 mg/kg/day) was received for 21 days. Step-through passive avoidance and Y-maze tests were performed to examine the effects of treatment on learning and memory impairments. Acetylcholine (Ach) levels and acetylcholinesterase (AchE) activity were measured via an enzyme-linked immunosorbent assay (ELISA). Levels of choline acetyltransferase (ChAT), nerve growth factor (NGF), cAMP response element-binding protein (CREB), and apoptosis-related protein expression were determined via Western blot analysis. EGFO pretreatment significantly attenuated scopolamine-induced memory impairments, relative to findings observed in the scopolamine-treated group. Levels of cholinergic factors in the brain tissues were markedly attenuated in the scopolamine-treated group. EGFO treatment also attenuated neural apoptosis in scopolamine-treated mice by decreasing the expression of apoptosis-related proteins such as Bax, Bcl2, cleaved caspase-3, and TUNEL staining. These results suggest that EGFO improves memory and cognition in a mouse model of memory impairment by restoring cholinergic and anti-apoptotic activity, possibly via activation of CREB/NGF signaling.

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NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice

Behavioral and Brain Functions ◽

10.1186/s12993-021-00185-x ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Dan Sun ◽

Guofang Gao ◽

Bihua Zhong ◽

Han Zhang ◽

Shixin Ding ◽

...

Keyword(s):

Learning And Memory ◽

Aging Process ◽

Brain Aging ◽

Neuronal Damage ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Receptor Protein ◽

Inflammasome Activation ◽

Histological Changes ◽

Memory Impairments ◽

Nlrp1 Inflammasome

Abstract Background Brain aging is an important risk factor in many human diseases, such as Alzheimer’s disease (AD). The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. However, it is still unclear when and how the neuroinflammation appears in the brain during aging process. Methods In this study, we observed the alterations of learning and memory impairments, neuronal damage, NLRP1 inflammasome activation, ROS production and NOX2 expression in the young 6-month-old (6 M) mice, presenile 16 M mice, and older 20 M and 24 M mice. Results The results indicated that, compared to 6 M mice, the locomotor activity, learning and memory abilities were slightly decreased in 16 M mice, and were significantly decreased in 20 M and 24 M mice, especially in the 24 M mice. The pathological results also showed that there were no significant neuronal damages in 6 M and 16 M mice, while there were obvious neuronal damages in 20 M and 24 M mice, especially in the 24 M group. Consistent with the behavioral and histological changes in the older mice, the activity of β-galactosidase (β-gal), the levels of ROS and IL-1β, and the expressions of NLRP1, ASC, caspase-1, NOX2, p47phox and p22phox were significantly increased in the cortex and hippocampus in the older 20 M and 24 M mice. Conclusion Our study suggested that NLRP1 inflammasome activation may be closely involved in aging-related neuronal damage and may be an important target for preventing brain aging.

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Rosmarinic Acid Induces Proliferation Suppression of Hepatoma Cells Associated with NF-κB Signaling Pathway

10.21203/rs.3.rs-100929/v1 ◽

2020 ◽

Author(s):

Yanjun An ◽

Jiandong Zhao ◽

Yourui Zhang ◽

Wen Wu ◽

Jiangtao Hu ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cell ◽

Rosmarinic Acid ◽

Caspase 3 ◽

Migration And Invasion ◽

Drug Candidate ◽

Tunel Staining ◽

Phosphatidylinositol 3 Kinase ◽

Related Factors ◽

Related Proteins

Abstract Background: Rosmarinic acid (RA) is a natural phenolic compound that acts as a Fyn inhibitor by 53 homology modeling of the human Fyn structure. Therefore, the apoptosis mechanism related to NF-κB signaling pathway induced by RA in HepG2 was investigated. Methods: The cell growth, apoptosis, and proliferation of HepG2 regulated by various concentrations of RA were studied. The proteins expression of MMP-2, MMP-9, PI3K, AKT, NF-κB, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were detected. Results: RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expressions of invasion-related factors, such as matrix metalloproteinase (MMP)-2 and MMP-9. TUNEL staining revealed that RA resulted in a dose-dependent increase of HepG2 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl-2 was downregulated and that of the pro-apoptotic proteins Bax and cleaved caspase-3 was increased. In addition, we found that the phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor kappa B (NF-κB) signaling pathway was involved in RA-mediated inhibition of HepG2 cell metastasis. Conclusion: Our study identified that RA as a drug candidate for the treatment of HCC.

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Endogenous sulfur dioxide regulates hippocampal neuron apoptosis in developing epileptic rats and is associated with the PERK signaling pathway

Neuroscience Letters ◽

10.1016/j.neulet.2017.11.036 ◽

2018 ◽

Vol 665 ◽

pp. 22-28 ◽

Cited By ~ 3

Author(s):

Manman Niu ◽

Ying Han ◽

Qinrui Li ◽

Jing Zhang

Keyword(s):

Sulfur Dioxide ◽

Signaling Pathway ◽

Hippocampal Neuron ◽

Neuron Apoptosis

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Molecular Mechanism of ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuron Apoptosis in SPS Rats

10.21203/rs.3.rs-170376/v1 ◽

2021 ◽

Author(s):

liang han ◽

Yan hao Xu ◽

Yu xiu Shi

Keyword(s):

Mrna Expression ◽

Hippocampal Neurons ◽

Hippocampal Neuron ◽

Control Group ◽

Tunel Staining ◽

Apoptosis Rate ◽

Memory Disorder ◽

Caspase 12 ◽

Induced Apoptosis ◽

Neuron Apoptosis

Abstract Apoptosis of hippocampal neurons is one of the mechanisms of hippocampal atrophy in posttraumatic stress disorder (PTSD), and it is also one of the important reasons of memory disorder in PTSD patients. The endoplasmic reticulum stress (ERS) mediated by activated transcription factor 6α(ATF6α)/site 1 protease (S1P)/S2P is involved in cell apoptosis, but it is not clear whether it is involved in hippocampal neuron apoptosis caused by PTSD. The PTSD rat model was constructed by the single-prolonged stress (SPS) method. The experiment was divided into two parts: (1) Control group, SPS 1d group, SPS 7d group, SPS 14d group. (2) Control group, SPS 7d group, SPS 7d+AEBSF group, control+AEBSF group. 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) is an ATF6α pathway inhibitor. The expression of ATF6α, glucose regulated protein (GRP78), S1P, S2, C/EBP homologous protein (CHOP), caspase-12 protein and mRNA in the hippocampus of PTSD rats were detected by immunohistochemistry, Western blotting and qRT-PCR. The apoptosis of hippocampal neurons was detected by TUNEL staining. In experiment 1, the protein and mRNA expression of ATF6α, GRP78 increased gradually in SPS 1d group and SPS 7d group, but decreased in SPS 14d group(P<0.01). In experiment 2, compared with the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly increased in SPS 7d group(P<0.01). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly decreased after AEBSF pretreatment(P<0.01). SPS induces apoptosis of hippocampal neurons by activating ERS mediated by ATF6α, suggesting that ERS-induced apoptosis is involved in the occurrence of PTSD.

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Erteng-Sanjie Capsule Enhances Chemosensitivity of 5-Fluorouracil in Tumor-Bearing Nude Mice with Gastric Cancer by Inhibiting Notch1/Hes1 Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9980565 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Jing Zhou ◽

Shulan Hao ◽

Hao Guo ◽

Han Yu ◽

Zhi Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Microvessel Density ◽

Dose Group ◽

Caspase 3 ◽

Tumor Volume ◽

Control Group ◽

Tunel Staining ◽

High Dose ◽

Therapeutic Effects

Gastric cancer is one of the most common cancers worldwide. This study investigated the chemosensitivity-enhancing effects of Erteng-Sanjie capsule (ETSJC) in combination with 5-fluorouracil (5-FU) on gastric cancer and its possible underlying mechanisms. The study established a subcutaneous xenograft model of human gastric cancer. The animals were divided into five groups: the control group, the 5-FU group, the 5-FU + ETSJC low-dose group, the 5-FU + ETSJC medium-dose group, and the 5-FU + ETSJC high-dose group. The tumor volume and tumor weight were calculated. TUNEL staining was used to evaluate cell apoptosis. Immunohistochemical analysis was used to detect the expression of Ki67+ cells and the CD31+ microvessel density in tumors. Simultaneously, western blot analysis was applied to detect the expression of caspase-3, Bax, Bcl-2, Notch1, and Hes1 proteins. Compared with the control group, tumor volume and weight in the 5-FU and 5-FU + ETSJC groups were inhibited. Moreover, compared with the 5-FU group, tumor volume and weight were significantly inhibited in the 5-FU + ETSJC groups. The numbers of Ki67+ cells, CD31+ microvessel density, and the expression of Bcl-2, Notch1, and Hes1 proteins were markedly decreased in the combination group when compared with the chemotherapy alone group. The numbers of TUNEL+ cells and the expression of Bax and caspase-3 proteins were significantly increased in the 5-FU + ETSJC groups when compared with the 5-FU group. The therapeutic effects were demonstrated to be dose dependent. In conclusion, the findings of the study showed that ETSJC improved the chemosensitivity of 5-FU by blocking Notch1/Hes1 signaling pathway in gastric cancer-bearing mice.

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Oxidation Stress-Mediated MAPK Signaling Pathway Activation Induces Neuronal Loss in the CA1 and CA3 Regions of the Hippocampus of Mice Following Chronic Cold Exposure

Brain Sciences ◽

10.3390/brainsci9100273 ◽

2019 ◽

Vol 9 (10) ◽

pp. 273 ◽

Cited By ~ 2

Author(s):

Bin Xu ◽

Li-Min Lang ◽

Shuai Lian ◽

Jing-Ru Guo ◽

Jian-Fa Wang ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Cold Stress ◽

Signaling Pathway ◽

Cold Exposure ◽

Neuronal Apoptosis ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Tunel Staining ◽

Oxidation Stress ◽

Pathway Activation

Chronic stress can damage homeostasis and induce various primary diseases. Although chronic cold stress is becoming an increasing problem for people who must work or live in extreme environments, risk-induced diseases in the central nervous system remain unstudied. Male C57BL/6 mice were exposed to an environment of 4 °C, 3 h per day for 1, 2, and 3 weeks and homeostasis in the hippocampus and neuronal apoptosis were evaluated by Western blotting, immunohistochemistry, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunofluorescence. The phenomena of oxidation stress, MAPK signaling pathway activation, anti-oxidation protein release, neuronal apoptosis increases, and neuronal proliferation inhibition were demonstrated in the CA1 and CA3 regions of mouse hippocampal tissues following cold exposure. We speculated that these phenomena were mediated by the MAPK pathway and were closely linked with oxidative stress in the hippocampus. This study provides novel concepts regarding neurodegenerative diseases, suggesting that chronic cold stress may be a critical factor to induce neurodegenerative diseases.

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