[Retracted] Oral Administration of Gintonin Protects the Brains of Mice against Aβ‐Induced Alzheimer Disease Pathology: Antioxidant and Anti‐Inflammatory Effects

Ikram, Muhammad; Jo, Min Gi; Park, Tae‐Ju; Kim, Min Woo; Khan, Ibrahim; Jo, Myeung Hoon; Kim, Myeong Ok

doi:10.1155/2021/6635552

Cited by 24 publications

(18 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gintonin-induced BDNF/TrkB signaling pathway is linked to Akt phosphorylation (Figures 6 and 7). Thus, the last proposal is that activated Akt also might stimulate the expressions of Nrf2/HO1 protein to attenuate IAA-induced oxidative stress, supporting this notion that in previous reports we showed that gintonin increased the Nrf2/HO1 expressions under oxidative stress [33][34][35]. Additionally, phosphorylated Akt regulates other essential cellular responses, such as cell growth, proliferation, survival under mitochondrial dysfunctions, and attenuation of cell death [36].…”

Section: Discussionsupporting

confidence: 83%

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

et al. 2021

View full text Add to dashboard Cite

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

show abstract

Section: Discussionsupporting

confidence: 83%

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

et al. 2021

View full text Add to dashboard Cite

show abstract

“…To analyze the effects of cycloastragenol against the elevated oxidative stress, we checked the expression of LPO and ROS in the brain homogenates, as suggested previ-ously [44]. Our results showed elevated expression of LPO and ROS in the cortex and hippocampus compared to the control group.…”

Section: Effects Of Cycloastragenol Against the Oxidative-stress And Neurotrophic Factors In Aβ-injected Mice Brainsmentioning

confidence: 67%

Cycloastragenol, a Triterpenoid Saponin, Regulates Oxidative Stress, Neurotrophic Dysfunctions, Neuroinflammation and Apoptotic Cell Death in Neurodegenerative Conditions

Ikram

Choe

et al. 2021

Cells

Self Cite

View full text Add to dashboard Cite

Here, we have unveiled the effects of cycloastragenol against Aβ (Amyloid-beta)-induced oxidative stress, neurogenic dysfunction, activated mitogen-activated protein (MAP) kinases, and mitochondrial apoptosis in an Aβ-induced mouse model of Alzheimer’s disease (AD). The Aβ-induced mouse model was developed by the stereotaxic injection of amyloid-beta (5 μg/mouse/intracerebroventricular), and cycloastragenol was given at a dose of 20 mg/kg/day/p.o for 6 weeks daily. For the biochemical analysis, we used immunofluorescence and Western blotting. Our findings showed that the injection of Aβ elevated oxidative stress and reduced the expression of neurogenic markers, as shown by the reduced expression of brain-derived neurotrophic factor (BDNF) and the phosphorylation of its specific receptor tropomyosin receptor kinase B (p-TrKB). In addition, there was a marked reduction in the expression of NeuN (neuronal nuclear protein) in the Aβ-injected mice brains (cortex and hippocampus). Interestingly, the expression of Nrf2 (nuclear factor erythroid 2–related factor 2), HO-1 (heme oxygenase-1), p-TrKB, BDNF, and NeuN was markedly enhanced in the Aβ + Cycloastragenol co-treated mice brains. We have also evaluated the expressions of MAP kinases such as phospho c-Jun-N-terminal kinase (p-JNK), p-38, and phospho-extracellular signal-related kinase (ERK1/2) in the experimental groups, which suggested that the expression of p-JNK, p-P-38, and p-Erk were significantly upregulated in the Aβ-injected mice brains; interestingly, these markers were downregulated in the Aβ + Cycloastragenol co-treated mice brains. We also checked the expression of activated microglia and inflammatory cytokines, which showed that cycloastragenol reduced the activated microglia and inflammatory cytokines. Moreover, we evaluated the effects of cycloastragenol against mitochondrial apoptosis and memory dysfunctions in the experimental groups. The findings showed significant regulatory effects against apoptosis and memory dysfunction as revealed by the Morris water maze (MWM) test. Collectively, the findings suggested that cycloastragenol regulates oxidative stress, neurotrophic processes, neuroinflammation, apoptotic cell death, and memory impairment in the mouse model of AD.

show abstract

“…After completion of the treatments, the mice were anesthetized and sacrificed, and the brains were removed carefully; the cortical and hippocampal sections were separated. The tissues were homogenized in a PRO-PREPTM extraction solution (iNtRON Biotechnology, Dallas, TX, USA), followed by centrifugation at a speed of 13,000 rpm for 25 min at 4 • C The supernatant were collected and stored at −80 • C for further experiments, as performed previously [56,57].…”

Section: Protein Extraction and Homogenization Of The Brain Of Micementioning

confidence: 99%

Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

Ahmad

Ikram

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ1–42)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For the development of an AD mouse model, amyloid-beta (Aβ1–42, 5 µL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice’s brain by using a stereotaxic frame. After that, the mice were treated with Luteolin for two weeks at a dose of 80 mg/kg/day. To monitor the biochemical changes, we conducted western blotting and immunofluorescence analysis. According to our findings, the infusion of amyloid-beta activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental mice; these changes were significantly inhibited in Aβ1–42 + Luteolin-treated mice. Likewise, we also checked the expression of inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB p65 (Ser536), tissue necrosis factor (TNF-α), and Interleukin1-β (IL-1β), in Aβ1–42-injected mice brain, which was attenuated in Aβ1–42 + Luteolin-treated mice brains. Further, we investigated the expression of pro- and anti-apoptotic cell death markers such as Bax, Bcl-2, Caspase-3, and Cox-2, which was significantly reduced in Aβ1–42 + Lut-treated mice brains compared to the brains of the Aβ-injected group. The results also indicated that with the administration of Aβ1–42, the expression levels of β-site amyloid precursor protein cleaving enzyme (BACE-1) and amyloid-beta (Aβ1–42) were significantly enhanced, while they were reduced in Aβ1–42 + Luteolin-treated mice. We also checked the expression of synaptic markers such as PSD-95 and SNAP-25, which was significantly enhanced in Aβ1–42 + Lut-treated mice. To unveil the underlying factors responsible for the protective effects of Luteolin against AD, we used a specific JNK inhibitor, which suggested that Luteolin reduced Aβ-associated neuroinflammation and neurodegeneration via inhibition of JNK. Collectively, our results indicate that Luteolin could serve as a novel therapeutic agent against AD-like pathological changes in mice.

show abstract

[Retracted] Oral Administration of Gintonin Protects the Brains of Mice against Aβ‐Induced Alzheimer Disease Pathology: Antioxidant and Anti‐Inflammatory Effects

Cited by 24 publications

References 42 publications

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Cycloastragenol, a Triterpenoid Saponin, Regulates Oxidative Stress, Neurotrophic Dysfunctions, Neuroinflammation and Apoptotic Cell Death in Neurodegenerative Conditions

Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

Contact Info

Product

Resources

About