Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice

Abstract

The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time. BSYZ decreases the activity of acetylcholinesterase (AChE), and increases the activity of choline acetyltransferase (ChAT) and the concentration of acetylcholine (Ach) in both hippocampus and cortex. In addition, western blot results (Bcl-2, Bax and Caspase-3) and TUNEL staining show that BSYZ prevents neuron from apoptosis, and elevates the expression of neurotrophic factors, including nerve growth factor (NGF), postsynapticdensity 95 (PSD95) and synaptophysin (SYN), in both hippocampus and cortex. BSYZ also increases the protein expression of SIRT1 and alleviates ER stress-associated proteins (PERK, IRE-1α, eIF-2α, BIP, PDI and CHOP). These results indicate that the neuroprotective mechanism of BSYZ might be related with SIRT1/ER stress pathway.

Bushen‐Yizhi Formula Alleviates Neuroinflammation via Inhibiting NLRP3 Inflammasome Activation in a Mouse Model of Parkinson’s Disease

“…Aging is the main cause to lead the occurrence of AD and PD. BSYZ is usually used in the treatment of dementia and aging-related memory deficiency in China [ 23 ]. However, it remains unknown whether BSYZ is also effective for PD.…”

“…BSYZ, a traditional Chinese medicine, is composed of common Cnidium fruit, tree peony bark, ginseng root, Radix Polygoni Multiflori Preparata, Barbary wolfberry fruit, and Fructus Ligustri Lucidi. Our previous studies have confirmed that BSYZ has extensive neuroprotective effects such as antisenesce, antiapoptosis, and alleviation of oxidative stress in various Alzheimer's disease (AD) animal models [ 23 – 26 ]. Our recent investigation further demonstrated BSYZ is effective in reducing age-related neurodegenerative disorders via antineuroinflammation [ 27 ].…”

Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

“…Based on these studies, silibinin potentially acts on multiple targets to inhibit AD pathologies. However, the effects of In the present study, learning and memory deficits were assessed using the Y-maze test, novel object recognition test and Morris water maze test, which are widely used methods to investigate the behaviors of mice [17][18][19][20]. The contents of soluble and insoluble Aβ and Aβ plaques are increased in 6-month-old APP/PS1 mice, comparable to patients with AD [21,22].…”

Sugarcane (Saccharum officinarum L.) Top Extract Ameliorates Cognitive Decline in Senescence Model SAMP8 Mice: Modulation of Neural Development and Energy Metabolism

“…Therefore, modulation of neurotransmitter levels has been suggested as a therapeutic target, as evidenced by the use of serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors (AChEIs) for the treatment of cognitive impairment ( Recanatini and Valenti, 2004 ). Degeneration of catecholaminergic neurons (including dopaminergic and noradrenergic) seriously worsens in SAMP8 mice from 8 months on ( Karasawa et al, 1997 ), and significant decrease of ACh level has been observed in 3-month old SAMP8 mice hippocampi and cortices ( Zhang et al, 2017 ). Enhanced synaptic plasticity in the cerebral cortex of STEE-fed mice could be explained by the significant upregulation of Mbp , a major myelin protein and essential for saltatory nerve conduction, and of Syt1 , an important regulator of synaptic vesicle transport ( Fields, 2015 ; Schupp et al, 2016 ).…”