Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement

Guo, Jinhui; Li, Chang; Zhang, Xin; Pei, Sujuan; Yu, Meishuang; Gao, Jianlian

doi:10.3892/etm.2014.1885

Cited by 39 publications

(35 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have reported a number of mechanisms for the cell death and apoptosis of AD cells (2)(3)(4). However, the specific processes of apoptosis in AD have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…The main characteristic of AD is the formation of extracellular senile plaques, which include β-amyloid precursor protein (APP) and intracellular neurofibrillary tangles (2,3). The pathological mechanism underlying AD has been investigated for a number of years; however, the essential cause of the disease has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…The pathological mechanism underlying AD has been investigated for a number of years; however, the essential cause of the disease has not been fully elucidated. In previous years, increasing evidence has indicated that the mitochondrial pathway may trigger the apoptosis of cells in AD patients (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease

Jia¹,

Wang²,

Zhang³

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. In previous years, increasing evidence has indicated that paraptosis and mitochondrial-mediated apoptosis may be associated with Alzheimer's disease (AD). However, the association between paraptosis and mitochondrial-mediated apoptosis, and the pathological processes underlying AD, remain elusive. In the present study, the β-amyloid precursor protein gene, and the gene mutations PS1M146L and L286V, were transfected to an SH-SY5Y cell line to establish an AD cell model. Subsequently, an MTT assay was used to examine the cell viability of the AD cell model, while a TUNEL assay was employed to observe the number of positively stained apoptotic cells. Cytoplasmic vacuolization was examined using light microscopy and images were photographed. Furthermore, western blot analysis was utilized to detect the expression of golden biomarkers of the mitochondrial pathway, including Bcl-2 and Bax. The paraptosis inhibitor, cycloheximide, was selected to treat the AD model cells in order to observe the association between paraptosis and mitochondrial-mediated apoptosis. The results indicated that the decrease in the cell viability of the AD cells was initiated at 24 h, as compared with the normal cells (P<0.05). TUNEL-positive stained cells were observed at 48 h, which was later compared with the cell death initiation. In addition, examination of cytoplasmic vacuolization using microscopy indicated that there were a small number of paraptosis cells present at 24 h. The expression levels of Bcl-2 was significantly decreased, while Bax was significantly increased at 48 h. Furthermore, cycloheximide treatment was demonstrated to significantly increase Bcl-2 expression, while decreasing Bax expression (P>0.05). In conclusion, the occurrence of paraptosis was demonstrated in the early pathological stages of AD, which may subsequently damage the mitochondria and trigger mitochondrial pathway-mediated apoptosis. Thus, paraptosis may trigger programmed cell death directly, or indirectly through the regulation of Bcl-2 and Bax protein expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease

Jia¹,

Wang²,

Zhang³

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…22,23 Many molecular mechanisms have been proposed for such anticancer activity, Downloaded by [University of Cambridge] at 17:58 16 June 2016 6 including autophagy regulation. [24][25][26][27] Moreover, autophagy contributes to the neuronal protective effects of ginsenoside Rb1 and compound K. 28,29 However, there is currently no evidence showing a direct connection between autophagy and ginsenoside-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint

Zheng

Wang

et al. 2016

Autophagy

View full text Add to dashboard Cite

Modulation of autophagy has been increasingly regarded as a promising cancer therapeutic approach. In this study, we screened several ginsenosides extracted from Panax ginseng and identified ginsenoside Ro (Ro) as a novel autophagy inhibitor. Ro blocked the autophagosome-lysosome fusion process by raising lysosomal pH and attenuating lysosomal cathepsin activity, resulting in the accumulation of the autophagosome marker MAP1LC3B/LC3B and SQSTM1/p62 (sequestosome 1) in various esophageal cancer cell lines. More detailed studies demonstrated that Ro activated ESR2 (estrogen receptor 2), which led to the activation of NCF1/p47(PHOX) (neutrophil cytosolic factor 1), a subunit of NADPH oxidase, and subsequent reactive oxygen species (ROS) production. Treatment with siRNAs or inhibitors of the ESR2-NCF1-ROS axis, such as N-acetyl-L-cysteine (NAC), diphenyleneiodonium chloride (DPI), apocynin (ACN), Tiron, and Fulvestrant apparently decreased Ro-induced LC3B-II, GFP-LC3B puncta, and SQSTM1, indicating that ROS instigates autophagic flux inhibition triggered by Ro. More importantly, suppression of autophagy by Ro sensitized 5-fluorouracil (5-Fu)-induced cell death in chemoresistant esophageal cancer cells. 5-Fu induced prosurvival autophagy, and by inhibiting such autophagy, siRNAs against BECN1/beclin 1, ATG5, ATG7, and LC3B enhanced 5-Fu-induced autophagy-associated and apoptosis-independent cell death. We observed that Ro potentiates 5-Fu cytotoxicity via delaying CHEK1 (checkpoint kinase 1) degradation and downregulating DNA replication process, resulting in the delayed DNA repair and the accumulation of DNA damage. In summary, these data suggest that Ro is a novel autophagy inhibitor and could function as a potent anticancer agent in combination therapy to overcome chemoresistance.

show abstract

“…Ginsenoside compound K can also promote Aβ clearance in vitro, and was shown to exert anti‐inflammatory and neuroprotective effects in a rodent model of cerebral ischemia . Even though it has not been as extensively studied as ginsenoside Rb1, these reports demonstrate that in vivo enzymatic transformation of ginsenoside Rb1 into compound K, the major metabolite of all known ginsenosides able to reach the systemic circulation, may not necessarily be a disadvantage.…”

Section: Unveiling Natural Leadsmentioning

confidence: 99%

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

Matos

Macedo²,

Rauter

2017

Medicinal Research Reviews

View full text Add to dashboard Cite

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age-related amyloid diseases that affect millions of people worldwide. Broadly supported by epidemiological data, the higher incidence of AD among type 2 diabetic patients led to the recognition of T2D as a tangible risk factor for the development of AD. Indeed, there is now growing evidence on brain structural and functional abnormalities arising from brain insulin resistance and deficiency, ultimately highlighting the need for new approaches capable of preventing the development of AD in type 2 diabetic patients. This review provides an update on overlapping pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity, and even shared genetic background. These events will be presented as puzzle pieces put together, thus establishing potential therapeutic targets for drug discovery and development against T2D and diabetes-induced cognitive decline-a heavyweight contributor to the increasing incidence of dementia in developed countries. Hoping to pave the way in this direction, we will present some of the most promising and well-studied drug leads with potential against both pathologies, including their respective bioactivity reports, mechanisms of action, and structure-activity relationships.

show abstract

Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement

Cited by 39 publications

References 20 publications

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease

Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

Contact Info

Product

Resources

About