Abstract
Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, so the present study aimed to observe the effects of ginsenoside Rb1 on ER stress signaling pathways in high glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high glucose for 72h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 μM Rb1 for 72h protected the neurons against high glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated proteins including protein kinase RNA (PKR)-like ER kinase (PERK) and C/EBP homology protein (CHOP) and downregulation of Bcl-2 induced by high glucose. Moreover, Rb1 inhibited both the elevation of intracellular reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high glucose. In addition, the high glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress 4-phenylbutyric acid (4-PBA) and anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and mitochondrial dysfunction.
Highlights
Substantial evidence from epidemiological studies suggests that diabetes is an independent risk factor for cognitive dysfunction[1]
To investigate the possible neuroprotective effects of ginsenoside Rb1 on high glucose-induced neuronal damage, hippocampal neurons were treated with ginsenoside Rb1 (1μM) plus 50 mM high glucose for 72h
We investigated the effect of ginsenoside Rb1 on high glucose-induced apoptosis in cultured hippocampal neurons using the TUNEL staining
Summary
Substantial evidence from epidemiological studies suggests that diabetes is an independent risk factor for cognitive dysfunction[1]. The importance of chronic hyperglycaemia in pathogenesis of diabetic cognitive impairment has been well established, which can increase polyol pathway flux and oxidative stress[3], and enhance formation of advanced glycation end-products (AGEs) [4]and disturbances of neuronal Ca2+ homeostasis[5]. Both clinical studies and animal experiments revealed that diabetes-induced impairments in hippocampus are closely associated with cognitive deficits[6,7,8]. Therapeutic interventions targeting ER stress are receiving major attention as promising strategies in the treatment of diabetic cognitive impairment
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